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Helicobacter pylori, Experimental Autoimmune Encephalomyelitis, and Multiple Sclerosis

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Neuro-Immuno-Gastroenterology

Abstract

Helicobacter pylori (H. pylori) is a common human pathogen which has been implicated in the pathogenesis of peptic ulcer disease and stomach cancer. H. pylori colonizes the stomach of about half the globe’s population, and its decline in the developed world coincided temporally with an increase in autoimmune and inflammatory disease. The hygiene hypothesis or “old friends” hypothesis have been proposed to explain this inverse link. Indeed, while H. pylori affects the innate immune system and induces strong cellular and humoral immune responses, it also has developed the ability to induce strong regulatory immune mechanisms to allow its persistence; these include, but are not restricted to, regulatory T cells (Treg cells).

Epidemiological and experimental evidence suggests a protective effect on autoimmune and inflammatory conditions including asthma, inflammatory bowel disease, and multiple sclerosis. The mechanisms of this protective effect are likely to be complex and include Treg cells, other immunoregulatory processes, and other host- and H. pylori-associated factors. Some of these have been explored in studies in the experimental autoimmune encephalomyelitis models and are currently being investigated in multiple sclerosis.

On the other hand, a positive association has been found between H. pylori and neuromyelitis optica.

This chapter reviews and discusses the immune response to H. pylori, with emphasis with immunoregulatory mechanisms, its pathogenicity-associated genes, and the evidence for its effects on neuroinflammatory diseases.

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References

  1. Aebischer T, Bumann D, Epple HJ, Metzger W, Schneider T, Cherepnev G, Walduck AK, Kunkel D, Moos V, Loddenkemper C, Jiadze I, Panasyuk M, Stolte M, Graham DY, Zeitz M, Meyer TF. Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines. Gut. 2008;57(8):1065–72. doi:10.1136/gut.2007.145839.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ai TL, Solomon BD, Hsieh CS. T-cell selection and intestinal homeostasis. Immunol Rev. 2014;259(1):60–74. doi:10.1111/imr.12171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Algood HM, Gallo-Romero J, Wilson KT, Peek Jr RM, Cover TL. Host response to Helicobacter pylori infection before initiation of the adaptive immune response. FEMS Immunol Med Microbiol. 2007;51(3):577–86. doi:10.1111/j.1574-695X.2007.00338.x.

    Article  CAS  PubMed  Google Scholar 

  4. Allen LA, Beecher BR, Lynch JT, Rohner OV, Wittine LM. Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release. J Immunol. 2005;174(6):3658–67.

    Article  CAS  PubMed  Google Scholar 

  5. Amedei A, Cappon A, Codolo G, Cabrelle A, Polenghi A, Benagiano M, Tasca E, Azzurri A, D’Elios MM, Del Prete G, de Bernard M. The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses. J Clin Invest. 2006;116(4):1092–101. doi:10.1172/JCI27177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Amedei A, Codolo G, Del Prete G, de Bernard M, D’Elios MM. The effect of Helicobacter pylori on asthma and allergy. J Asthma Allergy. 2010;3:139–47. doi:10.2147/JAA.S8971.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A. Evasion of toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci U S A. 2005;102(26):9247–52. doi:10.1073/pnas.0502040102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Araujo MI, Hoppe BS, Medeiros Jr M, Carvalho EM. Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases. Mem Inst Oswaldo Cruz. 2004;99(5 Suppl 1):27–32.

    Article  CAS  PubMed  Google Scholar 

  9. Arnold IC, Dehzad N, Reuter S, Martin H, Becher B, Taube C, Muller A. Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. J Clin Invest. 2011;121(8):3088–3093. doi:45041 [pii] 10.1172/JCI45041.

  10. Arnold IC, Hitzler I, Muller A. The immunomodulatory properties of Helicobacter pylori confer protection against allergic and chronic inflammatory disorders. Front Cell Infect Microbiol. 2012;2:10. doi:10.3389/fcimb.2012.00010.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother. 2013;13(12 Suppl):3–9. doi:10.1586/14737175.2013.865866.

    Article  PubMed  CAS  Google Scholar 

  12. Atherton JC. The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. Annu Rev Pathol. 2006;1:63–96.

    Article  CAS  PubMed  Google Scholar 

  13. Atherton JC, Blaser MJ. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest. 2009;119(9):2475–87. doi:10.1172/JCI38605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Atherton JC, Cao P, Peek Jr RM, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270(30):17771–7.

    Article  CAS  PubMed  Google Scholar 

  15. Atherton JC, Peek Jr RM, Tham KT, Cover TL, Blaser MJ. Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology. 1997;112(1):92–9.

    Article  CAS  PubMed  Google Scholar 

  16. Backert S, Selbach M. Role of type IV secretion in Helicobacter pylori pathogenesis. Cell Microbiol. 2008;10(8):1573–81. doi:10.1111/j.1462-5822.2008.01156.x.

    Article  CAS  PubMed  Google Scholar 

  17. Baker D, Amor S. Mouse models of multiple sclerosis: lost in translation? Curr Pharm Des. 2015;21(18):2440–52.

    Article  CAS  PubMed  Google Scholar 

  18. Banatvala N, Mayo K, Megraud F, Jennings R, Deeks JJ, Feldman RA. The cohort effect and Helicobacter pylori. J Infect Dis. 1993;168(1):219–21.

    Article  CAS  PubMed  Google Scholar 

  19. Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I. Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. Lancet Neurol. 2015;14(3):263–73. doi:10.1016/S1474-4422(14)70267-4.

    Article  PubMed  Google Scholar 

  20. Bennett J, de Seze J, Lana-Peixoto M, Palace J, Waldman A, Schippling S, Tenembaum S, Banwell B, Greenberg B, Levy M, Fujihara K, Chan K, Kim H, Asgari N, Sato D, Saiz A, Wuerfel J, Zimmermann H, Green A, Villoslada P, Paul F, with the G-I, Br. Neuromyelitis optica and multiple sclerosis: seeing differences through optical coherence tomography. Mult Scler. 2015;21:678–88. doi:10.1177/1352458514567216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, Wekerle H, Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479(7374):538–41. doi:10.1038/nature10554.

    Article  CAS  PubMed  Google Scholar 

  22. Bergman MP, Engering A, Smits HH, van Vliet SJ, van Bodegraven AA, Wirth HP, Kapsenberg ML, Vandenbroucke-Grauls CM, van Kooyk Y, Appelmelk BJ. Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J Exp Med. 2004;200(8):979–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Beswick EJ, Pinchuk IV, Earley RB, Schmitt DA, Reyes VE. Role of gastric epithelial cell-derived transforming growth factor beta in reduced CD4+ T cell proliferation and development of regulatory T cells during Helicobacter pylori infection. Infect Immun. 2011;79(7):2737–45. doi:10.1128/IAI.01146-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bimczok D, Clements RH, Waites KB, Novak L, Eckhoff DE, Mannon PJ, Smith PD, Smythies LE. Human primary gastric dendritic cells induce a Th1 response to H. pylori. Mucosal Immunol. 2010;3(3):260–9. doi:10.1038/mi.2010.10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Blaser MJ, Chen Y, Reibman J. Does Helicobacter pylori protect against asthma and allergy? Gut. 2008;57(5):561–7.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995;55(10):2111–5.

    CAS  PubMed  Google Scholar 

  27. Boncristiano M, Paccani SR, Barone S, Ulivieri C, Patrussi L, Ilver D, Amedei A, D’Elios MM, Telford JL, Baldari CT. The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms. J Exp Med. 2003;198(12):1887–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Boziki M, Grigoriadis N, Deretzi G, Lagoudaki R, Lourbopoulos A, Panayotopoulou E, Sgouras D, Tascos N, Kountouras J. Helicobacter pylori immunomodulatory properties in a mouse model of multiple sclerosis. Immuno-Gastroenterol. 2012;1(1):34–9. doi:10.7178/ig.1.1.8.

    Google Scholar 

  29. Brandt S, Kwok T, Hartig R, Konig W, Backert S. NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci U S A. 2005;102(26):9300–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Budzynski J, Klopocka M. Brain-gut axis in the pathogenesis of Helicobacter pylori infection. World J Gastroenterol. 2014;20(18):5212–25. doi:10.3748/wjg.v20.i18.5212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Busiello I, Acquaviva R, Di Popolo A, Blanchard TG, Ricci V, Romano M, Zarrilli R. Helicobacter pylori gamma-glutamyltranspeptidase upregulates COX-2 and EGF-related peptide expression in human gastric cells. Cell Microbiol. 2004;6(3):255–67.

    Article  CAS  PubMed  Google Scholar 

  32. Caruso R, Fina D, Paoluzi OA, Del Vecchio Blanco G, Stolfi C, Rizzo A, Caprioli F, Sarra M, Andrei F, Fantini MC, MacDonald TT, Pallone F, Monteleone G. IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa. Eur J Immunol. 2008;38(2):470–8.

    Article  CAS  PubMed  Google Scholar 

  33. Chen Y, Blaser MJ. Inverse associations of Helicobacter pylori with asthma and allergy. Arch Intern Med. 2007;167(8):821–7.

    Article  PubMed  Google Scholar 

  34. Chevalier C, Thiberge JM, Ferrero RL, Labigne A. Essential role of Helicobacter pylori gamma-glutamyltranspeptidase for the colonization of the gastric mucosa of mice. Mol Microbiol. 1999;31(5):1359–72.

    Article  CAS  PubMed  Google Scholar 

  35. Codolo G, Mazzi P, Amedei A, Del Prete G, Berton G, D’Elios MM, de Bernard M. The neutrophil-activating protein of Helicobacter pylori down-modulates Th2 inflammation in ovalbumin-induced allergic asthma. Cell Microbiol. 2008;10(11):2355–63. CMI1217 [pii]. doi:10.1111/j.1462-5822.2008.01217.x.

    Google Scholar 

  36. Colquhoun A, Arnold M, Ferlay J, Goodman KJ, Forman D, Soerjomataram I. Global patterns of cardia and non-cardia gastric cancer incidence in 2012. Gut. 2015. doi:10.1136/gutjnl-2014-308915.

    PubMed  Google Scholar 

  37. Comerford I, Bunting M, Fenix K, Haylock-Jacobs S, Litchfield W, Harata-Lee Y, Turvey M, Brazzatti J, Gregor C, Nguyen P, Kara E, McColl SR. An immune paradox: how can the same chemokine axis regulate both immune tolerance and activation?: CCR6/CCL20: a chemokine axis balancing immunological tolerance and inflammation in autoimmune disease. Bioessays. 2010;32(12):1067–76. doi:10.1002/bies.201000063.

    Article  CAS  PubMed  Google Scholar 

  38. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–17. doi:10.1016/S0140-6736(08)61620-7.

    Article  CAS  PubMed  Google Scholar 

  39. Constantinescu CS, Farooqi N, O’Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol. 2011;164(4):1079–106. doi:10.1111/j.1476-5381.2011.01302.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Conteduca V, Sansonno D, Lauletta G, Russi S, Ingravallo G, Dammacco F. H. pylori infection and gastric cancer: state of the art (review). Int J Oncol. 2013;42(1):5–18. doi:10.3892/ijo.2012.1701.

    CAS  PubMed  Google Scholar 

  41. Cook KW, Crooks J, Hussain K, O’Brien K, Braitch M, Kareen H, Constantinescu CS, Robinson K, Gran B. Helicobacter pylori infection reduces disease severity in an experimental model of multiple sclerosis. Front Microbiol. 2015;8:52.

    Google Scholar 

  42. Cook KW, Letley DP, Ingram RJ, Staples E, Skjoldmose H, Atherton JC, Robinson K. CCL20/CCR6-mediated migration of regulatory T cells to the Helicobacter pylori-infected human gastric mucosa. Gut. 2014;63(10):1550–9. doi:10.1136/gutjnl-2013-306253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cover TL, Blanke SR. Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat Rev Microbiol. 2005;3(4):320–32. doi:10.1038/nrmicro1095.

    Article  CAS  PubMed  Google Scholar 

  44. Cover TL, Peek Jr RM. Diet, microbial virulence, and Helicobacter pylori-induced gastric cancer. Gut Microbes. 2013;4(6):482–93. doi:10.4161/gmic.26262.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Cullen TW, Giles DK, Wolf LN, Ecobichon C, Boneca IG, Trent MS. Helicobacter pylori versus the host: remodeling of the bacterial outer membrane is required for survival in the gastric mucosa. PLoS Pathog. 2011;7(12), e1002454. doi:10.1371/journal.ppat.1002454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. D’Elios MM, Appelmelk BJ, Amedei A, Bergman MP, Del Prete G. Gastric autoimmunity: the role of Helicobacter pylori and molecular mimicry. Trends Mol Med. 2004;10(7):316–23.

    Article  PubMed  CAS  Google Scholar 

  47. D’Elios MM, Codolo G, Amedei A, Mazzi P, Berton G, Zanotti G, Del Prete G, de Bernard M. Helicobacter pylori, asthma and allergy. FEMS Immunol Med Microbiol. 2009;56(1):1–8.

    Google Scholar 

  48. Das S, Suarez G, Beswick EJ, Sierra JC, Graham DY, Reyes VE. Expression of B7-H1 on gastric epithelial cells: its potential role in regulating T cells during Helicobacter pylori infection. J Immunol. 2006;176(5):3000–9.

    Article  CAS  PubMed  Google Scholar 

  49. Djavaheri-Mergny M, Accaoui MJ, Rouillard D, Wietzerbin J. Gamma-glutamyl transpeptidase activity mediates NF-kappaB activation through lipid peroxidation in human leukemia U937 cells. Mol Cell Biochem. 2002;232(1–2):103–11.

    Article  CAS  PubMed  Google Scholar 

  50. Drakes ML, Czinn SJ, Blanchard TG. Regulation of murine dendritic cell immune responses by Helicobacter felis antigen. Infect Immun. 2006;74(8):4624–33. doi:10.1128/IAI.00289-06.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dunn BE, Cohen H, Blaser MJ. Helicobacter pylori. Clin Microbiol Rev. 1997;10(4):720–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Eck M, Schmausser B, Scheller K, Toksoy A, Kraus M, Menzel T, Muller-Hermelink HK, Gillitzer R. CXC chemokines Gro(alpha)/IL-8 and IP-10/MIG in Helicobacter pylori gastritis. Clin Exp Immunol. 2000;122(2):192–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Edstrom M, Mellergard J, Mjosberg J, Jenmalm M, Vrethem M, Press R, Dahle C, Ernerudh J. Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood. Mult Scler. 2011;17(1):57–66. doi:10.1177/1352458510381256.

    Article  CAS  PubMed  Google Scholar 

  54. El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, Stanford JL, Mayne ST, Goedert J, Blot WJ, Fraumeni Jr JF, Chow WH. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology. 2003;124(5):1193–201.

    Article  CAS  PubMed  Google Scholar 

  55. Elhofy A, Depaolo RW, Lira SA, Lukacs NW, Karpus WJ. Mice deficient for CCR6 fail to control chronic experimental autoimmune encephalomyelitis. J Neuroimmunol. 2009;213(1–2):91–9. doi:10.1016/j.jneuroim.2009.05.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Enarsson K, Lundgren A, Kindlund B, Hermansson M, Roncador G, Banham AH, Lundin BS, Quiding-Jarbrink M. Function and recruitment of mucosal regulatory T cells in human chronic Helicobacter pylori infection and gastric adenocarcinoma. Clin Immunol. 2006;121(3):358–68.

    Article  CAS  PubMed  Google Scholar 

  57. Engler DB, Reuter S, van Wijck Y, Urban S, Kyburz A, Maxeiner J, Martin H, Yogev N, Waisman A, Gerhard M, Cover TL, Taube C, Muller A. Effective treatment of allergic airway inflammation with Helicobacter pylori immunomodulators requires BATF3-dependent dendritic cells and IL-10. Proc Natl Acad Sci U S A. 2014;111(32):11810–5. doi:10.1073/pnas.1410579111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Epplein M, Zheng W, Li H, Peek Jr RM, Correa P, Gao J, Michel A, Pawlita M, Cai Q, Xiang YB, Shu XO. Diet, Helicobacter pylori strain-specific infection, and gastric cancer risk among Chinese men. Nutr Cancer. 2014;66(4):550–7. doi:10.1080/01635581.2014.894096.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Ernst PB, Gold BD. The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol. 2000;54:615–40. doi:10.1146/annurev.micro.54.1.615.

    Article  CAS  PubMed  Google Scholar 

  60. Fabis Pedrini MJ, Seewann A, Bennett KA, Wood AJ, James I, Burton J, Marshall BJ, Carroll WM, Kermode AG. Helicobacter pylori infection as a protective factor against multiple sclerosis risk in females. J Neurol Neurosurg Psychiatry. 2015. doi:10.1136/jnnp-2014-309495.

    Google Scholar 

  61. Fehlings M, Drobbe L, Moos V, Renner Viveros P, Hagen J, Beigier-Bompadre M, Pang E, Belogolova E, Churin Y, Schneider T, Meyer TF, Aebischer T, Ignatius R. Comparative analysis of the interaction of Helicobacter pylori with human dendritic cells, macrophages, and monocytes. Infect Immun. 2012;80(8):2724–34. doi:10.1128/IAI.00381-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Figueiredo C, Van Doorn LJ, Nogueira C, Soares JM, Pinho C, Figueira P, Quint WG, Carneiro F. Helicobacter pylori genotypes are associated with clinical outcome in Portuguese patients and show a high prevalence of infections with multiple strains. Scand J Gastroenterol. 2001;36(2):128–35.

    Article  CAS  PubMed  Google Scholar 

  63. Figueiredo Soares T, Aguiar Rocha G, Camargos Rocha AM, Correa-Oliveira R, Martins-Filho OA, Teles Carvalho AS, Souto Bittencourt PF, Afonso Oliveira C, Ferreira Nogueira AM, Alvares Cabral MM, Caetano Faria AM, Queiroz DM. Differences in peripheral blood lymphocyte phenotypes between Helicobacter pylori-positive children and adults with duodenal ulcer. Clin Microbiol Infect. 2007;13(11):1083–8.

    Article  CAS  PubMed  Google Scholar 

  64. Fukuhara S, Matsuzaki J, Tsugawa H, Masaoka T, Miyoshi S, Mori H, Fukushima Y, Yasui M, Kanai T, Suzuki H. Mucosal expression of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori-infected mice. J Gastroenterol Hepatol. 2014;29 Suppl 4:53–9. doi:10.1111/jgh.12771.

    Article  CAS  PubMed  Google Scholar 

  65. Gavalas E, Kountouras J, Deretzi G, Boziki M, Grigoriadis N, Zavos C, Venizelos I. Helicobacter pylori and multiple sclerosis. J Neuroimmunol. 2007;188(1–2):187–9; author reply 190. doi:10.1016/j.jneuroim.2007.06.007.

    Google Scholar 

  66. Gebert B, Fischer W, Weiss E, Hoffmann R, Haas R. Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science. 2003;301(5636):1099–102.

    Article  CAS  PubMed  Google Scholar 

  67. Gobert AP, McGee DJ, Akhtar M, Mendz GL, Newton JC, Cheng Y, Mobley HL, Wilson KT. Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: a strategy for bacterial survival. Proc Natl Acad Sci U S A. 2001;98(24):13844–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Gong M, Ling SS, Lui SY, Yeoh KG, Ho B. Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology. 2010;139(2):564–73. doi:10.1053/j.gastro.2010.03.050.

    Article  CAS  PubMed  Google Scholar 

  69. Gorrell RJ, Guan J, Xin Y, Tafreshi MA, Hutton ML, McGuckin MA, Ferrero RL, Kwok T. A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system. Cell Microbiol. 2013;15(4):554–70. doi:10.1111/cmi.12055.

    Article  CAS  PubMed  Google Scholar 

  70. Graham DY, Opekun AR, Osato MS, El-Zimaity HM, Lee CK, Yamaoka Y, Qureshi WA, Cadoz M, Monath TP. Challenge model for Helicobacter pylori infection in human volunteers. Gut. 2004;53(9):1235–43. doi:10.1136/gut.2003.037499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Geijtenbeek TB. Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori. Nat Immunol. 2009;10(10):1081–8. doi:10.1038/ni.1778.

    Article  CAS  PubMed  Google Scholar 

  72. Hardbower DM, Peek Jr RM, Wilson KT. At the bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer. J Leukoc Biol. 2014;96(2):201–12. doi:10.1189/jlb.4BT0214-099R.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Heimesaat MM, Fischer A, Plickert R, Wiedemann T, Loddenkemper C, Gobel UB, Bereswill S, Rieder G. Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils. PLoS One. 2014;9(6), e100362. doi:10.1371/journal.pone.0100362.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Hida N, Shimoyama Jr T, Neville P, Dixon MF, Axon AT, Shimoyama Sr T, Crabtree JE. Increased expression of IL-10 and IL-12 (p40) mRNA in Helicobacter pylori infected gastric mucosa: relation to bacterial cag status and peptic ulceration. J Clin Pathol. 1999;52(9):658–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Higgins PD, Johnson LA, Luther J, Zhang M, Sauder KL, Blanco LP, Kao JY. Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: mucosal crosstalk between stomach and distal intestine. Inflamm Bowel Dis. 2011;17(6):1398–408. doi:10.1002/ibd.21489.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Hoeksema MA, Scicluna BP, Boshuizen MC, van der Velden S, Neele AE, Van den Bossche J, Matlung HL, van den Berg TK, Goossens P, de Winther MP. IFN-gamma priming of macrophages represses a part of the inflammatory program and attenuates neutrophil recruitment. J Immunol. 2015. doi:10.4049/jimmunol.1402077.

    PubMed  Google Scholar 

  77. Hughes AM, Lucas RM, McMichael AJ, Dwyer T, Pender MP, van der Mei I, Taylor BV, Valery P, Chapman C, Coulthard A, Dear K, Kilpatrick TJ, Williams D, Ponsonby AL. Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially. Clin Exp Immunol. 2013;172(3):466–74. doi:10.1111/cei.12077.

    Article  PubMed  PubMed Central  Google Scholar 

  78. IARC. Schistosomes, liver flukes and Helicobacter pylori, vol. 61. Lyon: IARC Monogr Eval Carcinog Risks Hum. IARC; 1994.

    Google Scholar 

  79. Induruwa I, Constantinescu CS, Gran B. Fatigue in multiple sclerosis – a brief review. J Neurol Sci. 2012;323(1–2):9–15. doi:10.1016/j.jns.2012.08.007.

    Article  PubMed  Google Scholar 

  80. International Multiple Sclerosis Genetics C, Wellcome Trust Case Control C, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, Edkins S, Gray E, Booth DR, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, D’Alfonso S, Blackburn H, Martinelli Boneschi F, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker K, Baranzini SE, Bergamaschi L, Bergamaschi R, Bernstein A, Berthele A, Boggild M, Bradfield JP, Brassat D, Broadley SA, Buck D, Butzkueven H, Capra R, Carroll WM, Cavalla P, Celius EG, Cepok S, Chiavacci R, Clerget-Darpoux F, Clysters K, Comi G, Cossburn M, Cournu-Rebeix I, Cox MB, Cozen W, Cree BA, Cross AH, Cusi D, Daly MJ, Davis E, de Bakker PI, Debouverie M, D’Hooghe MB, Dixon K, Dobosi R, Dubois B, Ellinghaus D, Elovaara I, Esposito F, Fontenille C, Foote S, Franke A, Galimberti D, Ghezzi A, Glessner J, Gomez R, Gout O, Graham C, Grant SF, Guerini FR, Hakonarson H, Hall P, Hamsten A, Hartung HP, Heard RN, Heath S, Hobart J, Hoshi M, Infante-Duarte C, Ingram G, Ingram W, Islam T, Jagodic M, Kabesch M, Kermode AG, Kilpatrick TJ, Kim C, Klopp N, Koivisto K, Larsson M, Lathrop M, Lechner-Scott JS, Leone MA, Leppa V, Liljedahl U, Bomfim IL, Lincoln RR, Link J, Liu J, Lorentzen AR, Lupoli S, Macciardi F, Mack T, Marriott M, Martinelli V, Mason D, McCauley JL, Mentch F, Mero IL, Mihalova T, Montalban X, Mottershead J, Myhr KM, Naldi P, Ollier W, Page A, Palotie A, Pelletier J, Piccio L, Pickersgill T, Piehl F, Pobywajlo S, Quach HL, Ramsay PP, Reunanen M, Reynolds R, Rioux JD, Rodegher M, Roesner S, Rubio JP, Ruckert IM, Salvetti M, Salvi E, Santaniello A, Schaefer CA, Schreiber S, Schulze C, Scott RJ, Sellebjerg F, Selmaj KW, Sexton D, Shen L, Simms-Acuna B, Skidmore S, Sleiman PM, Smestad C, Sorensen PS, Sondergaard HB, Stankovich J, Strange RC, Sulonen AM, Sundqvist E, Syvanen AC, Taddeo F, Taylor B, Blackwell JM, Tienari P, Bramon E, Tourbah A, Brown MA, Tronczynska E, Casas JP, Tubridy N, Corvin A, Vickery J, Jankowski J, Villoslada P, Markus HS, Wang K, Mathew CG, Wason J, Palmer CN, Wichmann HE, Plomin R, Willoughby E, Rautanen A, Winkelmann J, Wittig M, Trembath RC, Yaouanq J, Viswanathan AC, Zhang H, Wood NW, Zuvich R, Deloukas P, Langford C, Duncanson A, Oksenberg JR, Pericak-Vance MA, Haines JL, Olsson T, Hillert J, Ivinson AJ, De Jager PL, Peltonen L, Stewart GJ, Hafler DA, Hauser SL, McVean G, Donnelly P, Compston A. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214–9. doi:10.1038/nature10251.

    Article  CAS  Google Scholar 

  81. Jarius S, Paul F, Ruprecht K, Wildemann B. Low vitamin B12 levels and gastric parietal cell antibodies in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders. J Neurol. 2012;259(12):2743–5. doi:10.1007/s00415-012-6677-1.

    Article  CAS  PubMed  Google Scholar 

  82. Kao JY, Zhang M, Miller MJ, Mills JC, Wang B, Liu M, Eaton KA, Zou W, Berndt BE, Cole TS, Takeuchi T, Owyang SY, Luther J. Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice. Gastroenterology. 2010;138(3):1046–54. doi:10.1053/j.gastro.2009.11.043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Khamri W, Walker MM, Clark P, Atherton JC, Thursz MR, Bamford KB, Lechler RI, Lombardi G. Helicobacter pylori stimulates dendritic cells to induce interleukin-17 expression from CD4+ T lymphocytes. Infect Immun. 2010;78(2):845–53. doi:10.1128/IAI.00524-09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kidd M, Lastovica AJ, Atherton JC, Louw JA. Heterogeneity in the Helicobacter pylori vacA and cagA genes: association with gastroduodenal disease in South Africa? Gut. 1999;45(4):499–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kido M, Watanabe N, Aoki N, Iwamoto S, Nishiura H, Maruoka R, Ikeda A, Azuma T, Chiba T. Dual roles of CagA protein in Helicobacter pylori-induced chronic gastritis in mice. Biochem Biophys Res Commun. 2011;412(2):266–72. doi:10.1016/j.bbrc.2011.07.081.

    Article  CAS  PubMed  Google Scholar 

  86. Kim JM, Kim JS, Yoo DY, Ko SH, Kim N, Kim H, Kim YJ. Stimulation of dendritic cells with Helicobacter pylori vacuolating cytotoxin negatively regulates their maturation via the restoration of E2F1. Clin Exp Immunol. 2011;166(1):34–45. doi:10.1111/j.1365-2249.2011.04447.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kodaman N, Pazos A, Schneider BG, Piazuelo MB, Mera R, Sobota RS, Sicinschi LA, Shaffer CL, Romero-Gallo J, de Sablet T, Harder RH, Bravo LE, Peek Jr RM, Wilson KT, Cover TL, Williams SM, Correa P. Human and Helicobacter pylori coevolution shapes the risk of gastric disease. Proc Natl Acad Sci U S A. 2014;111(4):1455–60. doi:10.1073/pnas.1318093111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Krakowiak MS, Noto JM, Piazuelo MB, Hardbower DM, Romero-Gallo J, Delgado A, Chaturvedi R, Correa P, Wilson KT, Peek Jr RM. Matrix metalloproteinase 7 restrains Helicobacter pylori-induced gastric inflammation and premalignant lesions in the stomach by altering macrophage polarization. Oncogene. 2014. doi:10.1038/onc.2014.135.

    PubMed  PubMed Central  Google Scholar 

  89. Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, Konig W, Backert S. Helicobacter exploits integrin for type IV secretion and kinase activation. Nature. 2007;449(7164):862–6. doi:10.1038/nature06187.

    Article  CAS  PubMed  Google Scholar 

  90. Lebwohl B, Blaser MJ, Ludvigsson JF, Green PH, Rundle A, Sonnenberg A, Genta RM. Decreased risk of celiac disease in patients with Helicobacter pylori colonization. Am J Epidemiol. 2013;178(12):1721–30. doi:10.1093/aje/kwt234.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4615–22. doi:10.1073/pnas.1000082107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Leunk RD, Johnson PT, David BC, Kraft WG, Morgan DR. Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. J Med Microbiol. 1988;26(2):93–9.

    Article  CAS  PubMed  Google Scholar 

  93. Li W, Minohara M, Piao H, Matsushita T, Masaki K, Matsuoka T, Isobe N, Su JJ, Ohyagi Y, Kira J. Association of anti-Helicobacter pylori neutrophil-activating protein antibody response with anti-aquaporin-4 autoimmunity in Japanese patients with multiple sclerosis and neuromyelitis optica. Mult Scler. 2009;15(12):1411–21. doi:10.1177/1352458509348961.

    Article  CAS  PubMed  Google Scholar 

  94. Li W, Minohara M, Su JJ, Matsuoka T, Osoegawa M, Ishizu T, Kira J. Helicobacter pylori infection is a potential protective factor against conventional multiple sclerosis in the Japanese population. J Neuroimmunol. 2007;184(1–2):227–31.

    Article  CAS  PubMed  Google Scholar 

  95. Lindgren A, Yun CH, Sjoling A, Berggren C, Sun JB, Jonsson E, Holmgren J, Svennerholm AM, Lundin SB. Impaired IFN-gamma production after stimulation with bacterial components by natural killer cells from gastric cancer patients. Exp Cell Res. 2011;317(6):849–58. doi:10.1016/j.yexcr.2011.01.006.

    Article  CAS  PubMed  Google Scholar 

  96. Liston A, Kohler RE, Townley S, Haylock-Jacobs S, Comerford I, Caon AC, Webster J, Harrison JM, Swann J, Clark-Lewis I, Korner H, McColl SR. Inhibition of CCR6 function reduces the severity of experimental autoimmune encephalomyelitis via effects on the priming phase of the immune response. J Immunol. 2009;182(5):3121–30. doi:10.4049/jimmunol.0713169.

    Article  CAS  PubMed  Google Scholar 

  97. Liu Y, Carlsson R, Comabella M, Wang J, Kosicki M, Carrion B, Hasan M, Wu X, Montalban X, Dziegiel MH, Sellebjerg F, Sorensen PS, Helin K, Issazadeh-Navikas S. FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS. Nat Med. 2014;20(3):272–82. doi:10.1038/nm.3485.

    Article  CAS  PubMed  Google Scholar 

  98. Long Y, Gao C, Qiu W, Hu X, Shu Y, Peng F, Lu Z. Helicobacter pylori infection in Neuromyelitis Optica and Multiple Sclerosis. Neuroimmunomodulation. 2013;20(2):107–12. doi:10.1159/000345838.

    Article  CAS  PubMed  Google Scholar 

  99. Lovett-Racke AE, Yang Y, Racke MK. Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis? Biochim Biophys Acta. 2011;1812(2):246–51. doi:10.1016/j.bbadis.2010.05.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ, Wolinsky JS, Balcer LJ, Banwell B, Barkhof F, Bebo Jr B, Calabresi PA, Clanet M, Comi G, Fox RJ, Freedman MS, Goodman AD, Inglese M, Kappos L, Kieseier BC, Lincoln JA, Lubetzki C, Miller AE, Montalban X, O’Connor PW, Petkau J, Pozzilli C, Rudick RA, Sormani MP, Stuve O, Waubant E, Polman CH. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278–86. doi:10.1212/WNL.0000000000000560.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Lundgren A, Stromberg E, Sjoling A, Lindholm C, Enarsson K, Edebo A, Johnsson E, Suri-Payer E, Larsson P, Rudin A, Svennerholm AM, Lundin BS. Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infect Immun. 2005;73(1):523–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Luther J, Owyang SY, Takeuchi T, Cole TS, Zhang M, Liu M, Erb-Downward J, Rubenstein JH, Chen CC, Pierzchala AV, Paul JA, Kao JY. Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis. Gut. 2011;60(11):1479–86. doi:10.1136/gut.2010.220087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Macarthur M, Hold GL, El-Omar EM. Inflammation and Cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. Am J Physiol Gastrointest Liver Physiol. 2004;286(4):G515–20.

    Article  CAS  PubMed  Google Scholar 

  104. Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015;14(2):183–93. doi:10.1016/S1474-4422(14)70256-X.

    Article  CAS  PubMed  Google Scholar 

  105. Malaty HM. Epidemiology of Helicobacter pylori infection. In: Sutton P, Mitchell HM, editors. Helicobacter pylori in the 21st century. Oxfordshire: CABI; 2010. p. 1–12.

    Chapter  Google Scholar 

  106. Matricardi PM, Rosmini F, Riondino S, Fortini M, Ferrigno L, Rapicetta M, Bonini S. Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study. BMJ. 2000;320(7232):412–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Matsukawa Y, Asai Y, Kitamura N, Sawada S, Kurosaka H. Exacerbation of rheumatoid arthritis following Helicobacter pylori eradication: disruption of established oral tolerance against heat shock protein? Med Hypotheses. 2005;64(1):41–3.

    Article  PubMed  Google Scholar 

  108. Matsuzaki J, Suzuki H, Minegishi Y, Sugai E, Tsugawa H, Yasui M, Hibi T. Acid suppression by proton pump inhibitors enhances aquaporin-4 and KCNQ1 expression in gastric fundic parietal cells in mouse. Dig Dis Sci. 2010;55(12):3339–48. doi:10.1007/s10620-010-1167-8.

    Article  CAS  PubMed  Google Scholar 

  109. Mayo L, Trauger SA, Blain M, Nadeau M, Patel B, Alvarez JI, Mascanfroni ID, Yeste A, Kivisakk P, Kallas K, Ellezam B, Bakshi R, Prat A, Antel JP, Weiner HL, Quintana FJ. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat Med. 2014;20(10):1147–56. doi:10.1038/nm.3681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Memon AA, Hussein NR, Miendje Deyi VY, Burette A, Atherton JC. Vacuolating cytotoxin genotypes are strong markers of gastric cancer and duodenal ulcer-associated Helicobacter pylori strains: a matched case-control study. J Clin Microbiol. 2014;52(8):2984–9. doi:10.1128/JCM.00551-14.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Miehlke S, Kirsch C, Agha-Amiri K, Gunther T, Lehn N, Malfertheiner P, Stolte M, Ehninger G, Bayerdorffer E. The Helicobacter pylori vacA s1, m1 genotype and cagA is associated with gastric carcinoma in Germany. Int J Cancer. 2000;87(3):322–7.

    Article  CAS  PubMed  Google Scholar 

  112. Mizuno H, Sato S, Ohnishi Y, Takahashi T, Nakashima I, Fujihara K, Aoki M, Ohnuma A. A case of myelitis with anti-aquaporin 4 antibody concomitant with immune thrombocytopenic purpura. Rinsho Shinkeigaku. 2014;54(3):195–9.

    Article  PubMed  Google Scholar 

  113. Mohebi N, Mamarabadi M, Moghaddasi M. Relation of Helicobacter pylori infection and multiple sclerosis in Iranian patients. Neurol Int. 2013;5(2):31–3. doi:10.4081/ni.2013.e10.

    Article  PubMed  Google Scholar 

  114. Molinari M, Salio M, Galli C, Norais N, Rappuoli R, Lanzavecchia A, Montecucco C. Selective inhibition of Ii-dependent antigen presentation by Helicobacter pylori toxin VacA. J Exp Med. 1998;187(1):135–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Montgomery SM, Lambe M, Olsson T, Ekbom A. Parental age, family size, and risk of multiple sclerosis. Epidemiology. 2004;15(6):717–23.

    Article  PubMed  Google Scholar 

  116. Moran AP, Lindner B, Walsh EJ. Structural characterization of the lipid A component of Helicobacter pylori rough- and smooth-form lipopolysaccharides. J Bacteriol. 1997;179(20):6453–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Mortimer K, Brown A, Feary J, Jagger C, Lewis S, Antoniak M, Pritchard D, Britton J. Dose-ranging study for trials of therapeutic infection with Necator americanus in humans. Am J Trop Med Hyg. 2006;75(5):914–20.

    CAS  PubMed  Google Scholar 

  118. Muhl H, Bachmann M, Pfeilschifter J. Inducible NO synthase and antibacterial host defence in times of Th17/Th22/T22 immunity. Cell Microbiol. 2011;13(3):340–8. doi:10.1111/j.1462-5822.2010.01559.x.

    Article  PubMed  CAS  Google Scholar 

  119. Munari F, Fassan M, Capitani N, Codolo G, Vila-Caballer M, Pizzi M, Rugge M, Della Bella C, Troilo A, D’Elios S, Baldari CT, D’Elios MM, de Bernard M. Cytokine BAFF released by Helicobacter pylori-infected macrophages triggers the Th17 response in human chronic gastritis. J Immunol. 2014;193(11):5584–94. doi:10.4049/jimmunol.1302865.

    Article  CAS  PubMed  Google Scholar 

  120. Murphy AC, Lalor SJ, Lynch MA, Mills KH. Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis. Brain Behav Immun. 2010;24(4):641–51. doi:10.1016/j.bbi.2010.01.014.

    Article  CAS  PubMed  Google Scholar 

  121. Nogueira C, Figueiredo C, Carneiro F, Gomes AT, Barreira R, Figueira P, Salgado C, Belo L, Peixoto A, Bravo JC, Bravo LE, Realpe JL, Plaisier AP, Quint WG, Ruiz B, Correa P, van Doorn LJ. Helicobacter pylori genotypes may determine gastric histopathology. Am J Pathol. 2001;158(2):647–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Nomura AM, Lee J, Stemmermann GN, Nomura RY, Perez-Perez GI, Blaser MJ. Helicobacter pylori CagA seropositivity and gastric carcinoma risk in a Japanese American population. J Infect Dis. 2002;186(8):1138–44. doi:10.1086/343808.

    Article  PubMed  Google Scholar 

  123. Nomura AM, Perez-Perez GI, Lee J, Stemmermann G, Blaser MJ. Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease. Am J Epidemiol. 2002;155(11):1054–9.

    Article  PubMed  Google Scholar 

  124. Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012;122(4):1180–8. doi:10.1172/JCI58649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. O’Keeffe J, Gately CM, O’Donoghue Y, Zulquernain SA, Stevens FM, Moran AP. Natural killer cell receptor T-lymphocytes in normal and Helicobacter pylori-infected human gastric mucosa. Helicobacter. 2008;13(6):500–5.

    Article  PubMed  Google Scholar 

  126. Ochoa-Reparaz J, Mielcarz DW, Wang Y, Begum-Haque S, Dasgupta S, Kasper DL, Kasper LH. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010;3(5):487–95. doi:10.1038/mi.2010.29.

    Article  CAS  PubMed  Google Scholar 

  127. Odenbreit S, Kavermann H, Puls J, Haas R. CagA tyrosine phosphorylation and interleukin-8 induction by Helicobacter pylori are independent from alpAB, HopZ and bab group outer membrane proteins. Int J Med Microbiol. 2002;292(3–4):257–66.

    Article  CAS  PubMed  Google Scholar 

  128. Oertli M, Noben M, Engler DB, Semper RP, Reuter S, Maxeiner J, Gerhard M, Taube C, Muller A. Helicobacter pylori gamma-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance. Proc Natl Acad Sci U S A. 2013;110(8):3047–52. doi:10.1073/pnas.1211248110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Oertli M, Sundquist M, Hitzler I, Engler DB, Arnold IC, Reuter S, Maxeiner J, Hansson M, Taube C, Quiding-Jarbrink M, Muller A. DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection. J Clin Invest. 2012;122(3):1082–96. 61029 [pii]. doi:10.1172/JCI61029.

    Google Scholar 

  130. Parkin DM. 11. Cancers attributable to infection in the UK in 2010. Br J Cancer. 2011;105 Suppl 2:S49–56. doi:10.1038/bjc.2011.484.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Paul F, Jarius S, Aktas O, Bluthner M, Bauer O, Appelhans H, Franciotta D, Bergamaschi R, Littleton E, Palace J, Seelig HP, Hohlfeld R, Vincent A, Zipp F. Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS Med. 2007;4(4), e133. doi:10.1371/journal.pmed.0040133.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Paziak-Domanska B, Chmiela M, Jarosinska A, Rudnicka W. Potential role of CagA in the inhibition of T cell reactivity in Helicobacter pylori infections. Cell Immunol. 2000;202(2):136–9.

    Article  CAS  PubMed  Google Scholar 

  133. Peek Jr RM, Fiske C, Wilson KT. Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol Rev. 2010;90(3):831–58. doi:10.1152/physrev.00039.2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Peek Jr RM, Miller GG, Tham KT, Perez-Perez GI, Zhao X, Atherton JC, Blaser MJ. Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. Lab Invest. 1995;73(6):760–70.

    CAS  PubMed  Google Scholar 

  135. Peleteiro B, Bastos A, Ferro A, Lunet N. Prevalence of Helicobacter pylori infection worldwide: a systematic review of studies with national coverage. Dig Dis Sci. 2014;59(8):1698–709. doi:10.1007/s10620-014-3063-0.

    Article  PubMed  Google Scholar 

  136. Pezeshki MZ, Zarrintan S, Zarrintan MH. Helicobacter pylori nanoparticles as a potential treatment of conventional multiple sclerosis. Med Hypotheses. 2008;70(6):1223. doi:10.1016/j.mehy.2007.12.008.

    Article  PubMed  Google Scholar 

  137. Pinto-Santini D, Salama NR. The biology of Helicobacter pylori infection, a major risk factor for gastric adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1853–8. doi:10.1158/1055-9965.EPI-04-0784.

    Article  CAS  PubMed  Google Scholar 

  138. Podda G, Nyirenda M, Crooks J, Gran B. Innate immune responses in the CNS: role of toll-like receptors, mechanisms, and therapeutic opportunities in multiple sclerosis. J Neuroimmune Pharmacol. 2013;8(4):791–806. doi:10.1007/s11481-013-9483-3.

    Article  PubMed  Google Scholar 

  139. Popova A, Kzhyshkowska J, Nurgazieva D, Goerdt S, Gratchev A. Pro- and anti-inflammatory control of M-CSF-mediated macrophage differentiation. Immunobiology. 2011;216(1–2):164–72. doi:10.1016/j.imbio.2010.06.003.

    Article  CAS  PubMed  Google Scholar 

  140. Quiding-Jarbrink M, Lundin BS, Lonroth H, Svennerholm AM. CD4+ and CD8+ T cell responses in Helicobacter pylori-infected individuals. Clin Exp Immunol. 2001;123(1):81–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Quiding-Jarbrink M, Raghavan S, Sundquist M. Enhanced M1 macrophage polarization in human Helicobacter pylori-associated atrophic gastritis and in vaccinated mice. PLoS One. 2010;5(11), e15018. doi:10.1371/journal.pone.0015018.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Quintana FJ, Patel B, Yeste A, Nyirenda M, Kenison J, Rahbari R, Fetco D, Hussain M, O’Mahony J, Magalhaes S, McGowan M, Johnson T, Rajasekharan S, Narayanan S, Arnold DL, Weiner HL, Banwell B, Bar-Or A, Canadian Pediatric Demyelinating Disease N. Epitope spreading as an early pathogenic event in pediatric multiple sclerosis. Neurology. 2014;83(24):2219–26. doi:10.1212/WNL.0000000000001066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Rad R, Brenner L, Bauer S, Schwendy S, Layland L, da Costa CP, Reindl W, Dossumbekova A, Friedrich M, Saur D, Wagner H, Schmid RM, Prinz C. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology. 2006;131(2):525–37.

    Article  CAS  PubMed  Google Scholar 

  144. Rhead JL, Letley DP, Mohammadi M, Hussein N, Mohagheghi MA, Eshagh Hosseini M, Atherton JC. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology. 2007;133(3):926–36.

    Article  CAS  PubMed  Google Scholar 

  145. Rimbara E, Mori S, Kim H, Shibayama K. Role of gamma-glutamyltranspeptidase in the pathogenesis of Helicobacter pylori infection. Microbiol Immunol. 2013;57(10):665–73. doi:10.1111/1348-0421.12089.

    Article  CAS  PubMed  Google Scholar 

  146. Robinson K, Argent RH, Atherton JC. The inflammatory and immune response to Helicobacter pylori infection. Best Pract Res Clin Gastroenterol. 2007;21(2):237–59.

    Article  CAS  PubMed  Google Scholar 

  147. Robinson K, Atherton J. Helicobacter pylori. In: Fratamico PM, Smith JL, Brogden KA, editors. Sequelae and long-term consequences of infectious diseases. Washington, DC: ASM Press; 2009. p. 107–33.

    Chapter  Google Scholar 

  148. Robinson K, Kenefeck R, Pidgeon EL, Shakib S, Patel S, Polson RJ, Zaitoun AM, Atherton JC. Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses. Gut. 2008;57(10):1375–85.

    Article  CAS  PubMed  Google Scholar 

  149. Rook GA. Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):5–15. doi:10.1007/s12016-011-8285-8.

    Article  CAS  PubMed  Google Scholar 

  150. Rook GA. Regulation of the immune system by biodiversity from the natural environment: an ecosystem service essential to health. Proc Natl Acad Sci U S A. 2013;110(46):18360–7. doi:10.1073/pnas.1313731110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Rubenstein JH, Inadomi JM, Scheiman J, Schoenfeld P, Appelman H, Zhang M, Metko V, Kao JY. Association between Helicobacter pylori and Barrett’s esophagus, erosive esophagitis, and gastroesophageal reflux symptoms. Clin Gastroenterol Hepatol. 2014;12(2):239–45. doi:10.1016/j.cgh.2013.08.029.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Rudi J, Kolb C, Maiwald M, Kuck D, Sieg A, Galle PR, Stremmel W. Diversity of Helicobacter pylori vacA and cagA genes and relationship to VacA and CagA protein expression, cytotoxin production, and associated diseases. J Clin Microbiol. 1998;36(4):944–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Rudnicka K, Matusiak A, Miszczyk E, Rudnicka W, Tenderenda M, Chmiela M. Immunophenotype of peripheral blood natural killer cells and IL-10 serum levels in relation to Helicobacter pylori status. APMIS. 2013;121(9):806–13. doi:10.1111/apm.12120.

    Article  CAS  PubMed  Google Scholar 

  154. Rudnicka K, Miszczyk E, Matusiak A, Walencka M, Moran AP, Rudnicka W, Chmiela M. Helicobacter pylori-driven modulation of NK cell expansion, intracellular cytokine expression and cytotoxic activity. Innate Immun. 2015;21(2):127–39. doi:10.1177/1753425913518225.

    Article  PubMed  CAS  Google Scholar 

  155. Sagar D, Lamontagne A, Foss CA, Khan ZK, Pomper MG, Jain P. Dendritic cell CNS recruitment correlates with disease severity in EAE via CCL2 chemotaxis at the blood-brain barrier through paracellular transmigration and ERK activation. J Neuroinflammation. 2012;9:245. doi:10.1186/1742-2094-9-245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Saito A, Yokohama A, Osaki Y, Ogawa Y, Nakahashi H, Toyama K, Mitsui T, Hashimoto Y, Koiso H, Uchiumi H, Saitoh T, Handa H, Sawamura M, Karasawa M, Murakami H, Tsukamoto N, Nojima Y. Circulating plasmacytoid dendritic cells in patients with primary and Helicobacter pylori-associated immune thrombocytopenia. Eur J Haematol. 2012;88(4):340–9. doi:10.1111/j.1600-0609.2011.01745.x.

    Article  CAS  PubMed  Google Scholar 

  157. Salama NR, Hartung ML, Muller A. Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol. 2013;11(6):385–99. doi:10.1038/nrmicro3016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Sawalha AH, Schmid WR, Binder SR, Bacino DK, Harley JB. Association between systemic lupus erythematosus and Helicobacter pylori seronegativity. J Rheumatol. 2004;31(8):1546–50.

    PubMed  Google Scholar 

  159. Saxena A, Martin-Blondel G, Mars LT, Liblau RS. Role of CD8 T cell subsets in the pathogenesis of multiple sclerosis. FEBS Lett. 2011;585(23):3758–63. doi:10.1016/j.febslet.2011.08.047.

    Article  CAS  PubMed  Google Scholar 

  160. Schmees C, Gerhard M, Treptau T, Voland P, Schwendy S, Rad R, Prinz C. VacA-associated inhibition of T-cell function: reviewed and reconsidered. Helicobacter. 2006;11(3):144–6. doi:10.1111/j.1523-5378.2006.00393.x.

    Article  CAS  PubMed  Google Scholar 

  161. Schmees C, Prinz C, Treptau T, Rad R, Hengst L, Voland P, Bauer S, Brenner L, Schmid RM, Gerhard M. Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase. Gastroenterology. 2007;132(5):1820–33.

    Article  CAS  PubMed  Google Scholar 

  162. Schwartz JT, Allen LA. Role of urease in megasome formation and Helicobacter pylori survival in macrophages. J Leukoc Biol. 2006;79(6):1214–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Seiskari T, Kondrashova A, Viskari H, Kaila M, Haapala AM, Aittoniemi J, Virta M, Hurme M, Uibo R, Knip M, Hyoty H. Allergic sensitization and microbial load – a comparison between Finland and Russian Karelia. Clin Exp Immunol. 2007;148(1):47–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Sellebjerg F, Krakauer M, Khademi M, Olsson T, Sorensen PS. FOXP3, CBLB and ITCH gene expression and cytotoxic T lymphocyte antigen 4 expression on CD4(+) CD25(high) T cells in multiple sclerosis. Clin Exp Immunol. 2012;170(2):149–55. doi:10.1111/j.1365-2249.2012.04654.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Serelli-Lee V, Ling KL, Ho C, Yeong LH, Lim GK, Ho B, Wong SB. Persistent Helicobacter pylori specific Th17 responses in patients with past H. pylori infection are associated with elevated gastric mucosal IL-1beta. PLoS One. 2012;7(6):e39199. doi:10.1371/journal.pone.0039199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Serrano C, Wright SW, Bimczok D, Shaffer CL, Cover TL, Venegas A, Salazar MG, Smythies LE, Harris PR, Smith PD. Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children. Mucosal Immunol. 2013;6(5):950–9. doi:10.1038/mi.2012.133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Sewald X, Gebert-Vogl B, Prassl S, Barwig I, Weiss E, Fabbri M, Osicka R, Schiemann M, Busch DH, Semmrich M, Holzmann B, Sebo P, Haas R. Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin. Cell Host Microbe. 2008;3(1):20–9. doi:10.1016/j.chom.2007.11.003.

    Article  CAS  PubMed  Google Scholar 

  168. Shi Y, Liu XF, Zhuang Y, Zhang JY, Liu T, Yin Z, Wu C, Mao XH, Jia KR, Wang FJ, Guo H, Flavell RA, Zhao Z, Liu KY, Xiao B, Guo Y, Zhang WJ, Zhou WY, Guo G, Zou QM. Helicobacter pylori-induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice. J Immunol. 2010;184(9):5121–9. doi:10.4049/jimmunol.0901115.

    Article  CAS  PubMed  Google Scholar 

  169. Smith SM. Role of toll-like receptors in Helicobacter pylori infection and immunity. World J Gastrointest Pathophysiol. 2014;5(3):133–46. doi:10.4291/wjgp.v5.i3.133.

    PubMed  PubMed Central  Google Scholar 

  170. Smith SM, Moran AP, Duggan SP, Ahmed SE, Mohamed AS, Windle HJ, O’Neill LA, Kelleher DP. Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide. J Immunol. 2011;186(4):2462–71. doi:10.4049/jimmunol.1000864.

    Article  CAS  PubMed  Google Scholar 

  171. Smyk DS, Koutsoumpas AL, Mytilinaiou MG, Rigopoulou EI, Sakkas LI, Bogdanos DP. Helicobacter pylori and autoimmune disease: cause or bystander. World J Gastroenterol. 2014;20(3):613–29. doi:10.3748/wjg.v20.i3.613.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  172. Sommer F, Faller G, Konturek P, Kirchner T, Hahn EG, Zeus J, Rollinghoff M, Lohoff M. Antrum- and corpus mucosa-infiltrating CD4(+) lymphocytes in Helicobacter pylori gastritis display a Th1 phenotype. Infect Immun. 1998;66(11):5543–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Sormani MP, Arnold DL, De Stefano N. Treatment effect on brain atrophy correlates with treatment effect on disability in multiple sclerosis. Ann Neurol. 2014;75(1):43–9. doi:10.1002/ana.24018.

    Article  PubMed  Google Scholar 

  174. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299(6710):1259–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Sundquist M, Quiding-Jarbrink M. Helicobacter pylori and its effect on innate and adaptive immunity: new insights and vaccination strategies. Expert Rev Gastroenterol Hepatol. 2010;4(6):733–44. doi:10.1586/egh.10.71.

    Article  CAS  PubMed  Google Scholar 

  176. Sundrud MS, Torres VJ, Unutmaz D, Cover TL. Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion. Proc Natl Acad Sci U S A. 2004;101(20):7727–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. t Hart BA, Gran B, Weissert R. EAE: imperfect but useful models of multiple sclerosis. Trends Mol Med. 2011;17(3):119–25. doi:10.1016/j.molmed.2010.11.006.

    Article  CAS  Google Scholar 

  178. Tan MP, Pedersen J, Zhan Y, Lew AM, Pearse MJ, Wijburg OL, Strugnell RA. CD8+ T cells are associated with severe gastritis in Helicobacter pylori-infected mice in the absence of CD4+ T cells. Infect Immun. 2008;76(3):1289–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Tanasescu R, Constantinescu CS. Helminth therapy for MS. Curr Top Behav Neurosci. 2014. doi:10.1007/7854_2014_361.

    Google Scholar 

  180. Tegtmeyer N, Wessler S, Backert S. Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis. FEBS J. 2011;278(8):1190–202. doi:10.1111/j.1742-4658.2011.08035.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Teymournejad O, Mobarez AM, Hassan ZM, Moazzeni SM, Ahmadabad HN. In vitro suppression of dendritic cells by Helicobacter pylori OipA. Helicobacter. 2014;19(2):136–43. doi:10.1111/hel.12107.

    Article  CAS  PubMed  Google Scholar 

  182. Torres VJ, VanCompernolle SE, Sundrud MS, Unutmaz D, Cover TL. Helicobacter pylori vacuolating cytotoxin inhibits activation-induced proliferation of human T and B lymphocyte subsets. J Immunol. 2007;179(8):5433–40.

    Article  CAS  PubMed  Google Scholar 

  183. Trujillo C, Erb KJ. Inhibition of allergic disorders by infection with bacteria or the exposure to bacterial products. Int J Med Microbiol. 2003;293(2–3):123–31.

    Article  CAS  PubMed  Google Scholar 

  184. Valsasina P, Rocca MA, Horsfield MA, Absinta M, Messina R, Caputo D, Comi G, Filippi M. Regional cervical cord atrophy and disability in multiple sclerosis: a voxel-based analysis. Radiology. 2013;266(3):853–61. doi:10.1148/radiol.12120813.

    Article  PubMed  Google Scholar 

  185. Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Memet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol. 2004;5(11):1166–74.

    Article  CAS  PubMed  Google Scholar 

  186. Vyse AJ, Gay NJ, Hesketh LM, Andrews NJ, Marshall B, Thomas HI, Morgan-Capner P, Miller E. The burden of Helicobacter pylori infection in England and Wales. Epidemiol Infect. 2002;128(3):411–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Wang SK, Zhu HF, He BS, Zhang ZY, Chen ZT, Wang ZZ, Wu GL. CagA+ H. pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis. World J Gastroenterol. 2007;13(21):2923–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Wei L, Wang J, Liu Y. Prior to Foxp3(+) regulatory T-cell induction, interleukin-10-producing B cells expand after Helicobacter pylori infection. Pathog Dis. 2014;72(1):45–54. doi:10.1111/2049-632X.12182.

    Article  CAS  PubMed  Google Scholar 

  189. Wender M. Prevalence of Helicobacter pylori infection among patients with multiple sclerosis. Neurol Neurochir Pol. 2003;37(1):45–8.

    PubMed  Google Scholar 

  190. Wilke CM, Bishop K, Fox D, Zou W. Deciphering the role of Th17 cells in human disease. Trends Immunol. 2011;32(12):603–11. doi:10.1016/j.it.2011.08.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Wilson KT, Crabtree JE. Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies. Gastroenterology. 2007;133(1):288–308.

    Article  CAS  PubMed  Google Scholar 

  192. Wu YY, Tsai HF, Lin WC, Hsu PI, Shun CT, Wu MS, Hsu PN. Upregulation of CCL20 and recruitment of CCR6+ gastric infiltrating lymphocytes in Helicobacter pylori gastritis. Infect Immun. 2007;75(9):4357–63. IAI.01660-06 [pii]. doi:10.1128/IAI.01660-06.

    Google Scholar 

  193. Wustner S, Mejias-Luque R, Koch MF, Rath E, Vieth M, Sieber SA, Haller D, Gerhard M. Helicobacter pylori gamma-glutamyltranspeptidase impairs T-lymphocyte function by compromising metabolic adaption through inhibition of cMyc and IRF4 expression. Cell Microbiol. 2015;17(1):51–61. doi:10.1111/cmi.12335.

    Article  PubMed  CAS  Google Scholar 

  194. Yamaoka Y, Kikuchi S, el-Zimaity HM, Gutierrez O, Osato MS, Graham DY. Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology. 2002;123(2):414–24.

    Article  CAS  PubMed  Google Scholar 

  195. Yamaoka Y, Kita M, Kodama T, Sawai N, Tanahashi T, Kashima K, Imanishi J. Chemokines in the gastric mucosa in Helicobacter pylori infection. Gut. 1998;42(5):609–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Yamaoka Y, Kwon DH, Graham DY. A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci U S A. 2000;97(13):7533–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Yamaoka Y, Ojo O, Fujimoto S, Odenbreit S, Haas R, Gutierrez O, El-Zimaity HM, Reddy R, Arnqvist A, Graham DY. Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut. 2006;55(6):775–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Yin YN, Wang CL, Liu XW, Cui Y, Xie N, Yu QF, Li FJ, Lu FG. Gastric and duodenum microflora analysis after long-term Helicobacter pylori infection in Mongolian Gerbils. Helicobacter. 2011;16(5):389–97. doi:10.1111/j.1523-5378.2011.00862.x.

    Article  PubMed  Google Scholar 

  199. Yoshimura S, Isobe N, Matsushita T, Masaki K, Sato S, Kawano Y, Ochi H, Kira J. Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients. PLoS One. 2014;9(4), e95367. doi:10.1371/journal.pone.0095367.

    Article  PubMed  PubMed Central  Google Scholar 

  200. Yoshimura S, Isobe N, Matsushita T, Yonekawa T, Masaki K, Sato S, Kawano Y, Kira J, South Japan Multiple Sclerosis Genetics C. Distinct genetic and infectious profiles in Japanese neuromyelitis optica patients according to anti-aquaporin 4 antibody status. J Neurol Neurosurg Psychiatry. 2013;84(1):29–34. doi:10.1136/jnnp-2012-302925.

    Article  PubMed  Google Scholar 

  201. Yoshimura S, Isobe N, Yonekawa T, Matsushita T, Masaki K, Sato S, Kawano Y, Yamamoto K, Kira J, South Japan Multiple Sclerosis Genetics C. Genetic and infectious profiles of Japanese multiple sclerosis patients. PLoS One. 2012;7(11), e48592. doi:10.1371/journal.pone.0048592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust and The University of Nottingham, Queen’s Medical Centre, Nottingham, UK

    Karen Robinson BSc, PhD

  2. Department of Clinical Microbiology, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK

    Joanna Stephens MBChB, MSc

  3. Department of Clinical Neuroscience, Queen’s Medical Centre, University Hospital, University of Nottingham, Nottingham, UK

    Cris S. Constantinescu MD, PhD

  4. Clinical Neurology Research Group, Division of Clinical Neuroscience, Queen’s Medical Centre, University of Nottingham School of Medicine, Nottingham, UK

    Bruno Gran MD, PhD

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  1. Karen Robinson BSc, PhD
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  3. Cris S. Constantinescu MD, PhD
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  4. Bruno Gran MD, PhD
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Correspondence to Karen Robinson BSc, PhD .

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  1. Neurology, C Floor South Block, University of Nottingham, Nottingham, United Kingdom

    Cris Constantinescu

  2. Atlantic Digestive Health Institute, Morristown Medical Center, Columbus, Ohio, USA

    Razvan Arsenescu

  3. Armedica LLC, Columbus, Ohio, USA

    Violeta Arsenescu

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Robinson, K., Stephens, J., Constantinescu, C.S., Gran, B. (2016). Helicobacter pylori, Experimental Autoimmune Encephalomyelitis, and Multiple Sclerosis. In: Constantinescu, C., Arsenescu, R., Arsenescu, V. (eds) Neuro-Immuno-Gastroenterology. Springer, Cham. https://doi.org/10.1007/978-3-319-28609-9_6

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