Advertisement

Immune Evasion Strategies and Persistence of Helicobacter pylori

  • Raquel Mejías-LuqueEmail author
  • Markus Gerhard
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 400)

Abstract

Helicobacter pylori infection is commonly acquired during childhood, can persist lifelong if not treated, and can cause different gastric pathologies, including chronic gastritis, peptic ulcer disease, and eventually gastric cancer. H. pylori has developed a number of strategies in order to cope with the hostile conditions found in the human stomach as well as successful mechanisms to evade the strong innate and adaptive immune responses elicited upon infection. Thus, by manipulating innate immune receptors and related signaling pathways, inducing tolerogenic dendritic cells and inhibiting effector T cell responses, H. pylori ensures low recognition by the host immune system as well as its persistence in the gastric epithelium. Bacterial virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin A, or gamma-glutamyltranspeptidase have been extensively studied in the context of bacterial immune escape and persistence. Further, the bacterium possesses other factors that contribute to immune evasion. In this chapter, we discuss in detail the main evasion and persistence strategies evolved by the bacterium as well as the specific bacterial virulence factors involved.

Keywords

H. pylori Immune evasion Persistence 

References

  1. Allen LA, Schlesinger LS, Kang B (2000) Virulent strains of Helicobacter pylori demonstrate delayed phagocytosis and stimulate homotypic phagosome fusion in macrophages. J Exp Med 191(1):115–128. doi: 10.1084/jem.191.1.115 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Allen LA, Beecher BR, Lynch JT, Rohner OV, Wittine LM (2005) Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release. J Immunol 174(6):3658–3667. doi: 10.4049/jimmunol.174.6.3658 CrossRefPubMedGoogle Scholar
  3. Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A (2005) Evasion of Toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci USA 102(26):9247–9252. doi: 10.1073/pnas.0502040102 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Appelmelk BJ, Vandenbroucke-Grauls C (2001) Lipopolysaccharide Lewis antigens. In: Mobley HLT, Mendz GL, Hazell SL (eds) Helicobacter pylori: physiology and genetics. Washington (DC). Chapter 35. ISBN-10: 1-55581-213-9Google Scholar
  5. Arnold IC, Lee JY, Amieva MR, Roers A, Flavell RA, Sparwasser T, Muller A (2011) Tolerance rather than immunity protects from Helicobacter pylori-induced gastric preneoplasia. Gastroenterology 140(1):199–209. doi: 10.1053/j.gastro.2010.06.047 CrossRefPubMedGoogle Scholar
  6. Bajaj-Elliott M, Fedeli P, Smith GV, Domizio P, Maher L, Ali RS, Quinn AG, Farthing MJ (2002) Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis. Gut 51(3):356–361. doi: 10.1136/gut.51.3.356 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bamford KB, Fan X, Crowe SE, Leary JF, Gourley WK, Luthra GK, Brooks EG, Graham DY, Reyes VE, Ernst PB (1998) Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. Gastroenterology 114(3):482–492. doi: 10.1016/S0016-5085(98)70531-1 CrossRefPubMedGoogle Scholar
  8. Bauer B, Pang E, Holland C, Kessler M, Bartfeld S, Meyer TF (2012) The Helicobacter pylori virulence effector CagA abrogates human beta-defensin 3 expression via inactivation of EGFR signaling. Cell Host Microbe 11(6):576–586. doi: 10.1016/j.chom.2012.04.013 CrossRefPubMedGoogle Scholar
  9. Bergman MP, Engering A, Smits HH, van Vliet SJ, van Bodegraven AA, Wirth H-P, Kapsenberg ML, Vandenbroucke-Grauls CMJE, van Kooyk Y, Appelmelk BJ (2004) 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 200(8):979–990. doi: 10.1084/jem.20041061 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Boncristiano M, Paccani SR, Barone S, Ulivieri C, Patrussi L, Ilver D, Amedei A, D’Elios MM, Telford JL, Baldari CT (2003) The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms. J Exp Med 198(12):1887–1897. doi: 10.1084/jem.20030621 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Cheng HH, Tseng GY, Yang HB, Wang HJ, Lin HJ, Wang WC (2012) Increased numbers of Foxp3-positive regulatory T cells in gastritis, peptic ulcer and gastric adenocarcinoma. World J Gastroenterol WJG 18(1):34–43. doi: 10.3748/wjg.v18.i1.34 CrossRefPubMedGoogle Scholar
  12. Cover TL, Glupczynski Y, Lage AP, Burette A, Tummuru MK, Perez-Perez GI, Blaser MJ (1995) Serologic detection of infection with cagA+ Helicobacter pylori strains. J Clin Microbiol 33(6):1496–1500 (0095-1137/95/$04.00)Google Scholar
  13. Cullen TW, Giles DK, Wolf LN, Ecobichon C, Boneca IG, Trent MS (2011) Helicobacter pylori versus the host: remodeling of the bacterial outer membrane is required for survival in the gastric mucosa. PLoS Pathog 7(12):e1002454. doi: 10.1371/journal.ppat.1002454 CrossRefPubMedPubMedCentralGoogle Scholar
  14. D’Elios MM, Manghetti M, De Carli M, Costa F, Baldari CT, Burroni D, Telford JL, Romagnani S, Del Prete G (1997) T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease. J Immunol 158(2):962–967PubMedGoogle Scholar
  15. Devi S, Rajakumara E, Ahmed N (2015) Induction of Mincle by Helicobacter pylori and consequent anti-inflammatory signaling denote a bacterial survival strategy. Sci Rep 5:15049. doi: 10.1038/srep15049 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Du SY, Wang HJ, Cheng HH, Chen SD, Wang LH, Wang WC (2014) Cholesterol glycosylation by Helicobacter pylori delays internalization and arrests phagosome maturation in macrophages. J Microbiol Immunol Infect (Wei mian yu gan ran za zhi). doi: 10.1016/j.jmii.2014.05.011
  17. Fan XJ, Chua A, Shahi CN, McDevitt J, Keeling PW, Kelleher D (1994) Gastric T lymphocyte responses to Helicobacter pylori in patients with H. pylori colonisation. Gut 35(10):1379–1384. doi: 10.1136/gut.35.10.1379 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Fowler M, Thomas RJ, Atherton J, Roberts IS, High NJ (2006) Galectin-3 binds to Helicobacter pylori O-antigen: it is upregulated and rapidly secreted by gastric epithelial cells in response to H. pylori adhesion. Cell Microbiol 8(1):44–54. doi: 10.1111/j.1462-5822.2005.00599.x CrossRefPubMedGoogle Scholar
  19. Ganten TM, Aravena E, Sykora J, Koschny R, Mohr J, Rudi J, Stremmel W, Walczak H (2007) Helicobacter pylori-induced apoptosis in T cells is mediated by the mitochondrial pathway independent of death receptors. Eur J Clin Invest 37(2):117–125. doi: 10.1111/j.1365-2362.2007.01761.x CrossRefPubMedGoogle Scholar
  20. Gebert B, Fischer W, Weiss E, Hoffmann R, Haas R (2003) Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science 301(5636):1099–1102. doi: 10.1126/science.1086871
  21. Gerhard M, Schmees C, Voland P, Endres N, Sander M, Reindl W, Rad R, Oelsner M, Decker T, Mempel M, Hengst L, Prinz C (2005) A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells. Gastroenterology 128(5):1327–1339. doi: 10.1053/j.gastro.2005.03.018 CrossRefPubMedGoogle Scholar
  22. Gewirtz AT, Yu Y, Krishna US, Israel DA, Lyons SL, Peek RM (2004) Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity. J Infect Dis 189(10):1914–1920. doi: 10.1086/386289 CrossRefPubMedGoogle Scholar
  23. Gobert AP, McGee DJ, Akhtar M, Mendz GL, Newton JC, Cheng Y, Mobley HL, Wilson KT (2001) Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: a strategy for bacterial survival. Proc Natl Acad Sci USA 98(24):13844–13849. doi: 10.1073/pnas.241443798 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Gobert AP, Cheng Y, Wang JY, Boucher JL, Iyer RK, Cederbaum SD, Casero RA Jr, Newton JC, Wilson KT (2002a) Helicobacter pylori induces macrophage apoptosis by activation of arginase II. J Immunol 168(9):4692–4700. doi: 10.4049/jimmunol.168.9.4692 CrossRefPubMedGoogle Scholar
  25. Gobert AP, Mersey BD, Cheng Y, Blumberg DR, Newton JC, Wilson KT (2002b) Cutting edge: urease release by Helicobacter pylori stimulates macrophage inducible nitric oxide synthase. J Immunol 168(12):6002–6006. doi: 10.4049/jimmunol.168.12.6002 CrossRefPubMedGoogle Scholar
  26. Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Geijtenbeek TB (2009) Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori. Nat Immunol 10(10):1081–1088. doi: 10.1038/ni.1778 CrossRefPubMedGoogle Scholar
  27. Hamanaka Y, Nakashima M, Wada A, Ito M, Kurazono H, Hojo H, Nakahara Y, Kohno S, Hirayama T, Sekine I (2001) Expression of human beta-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori. Gut 49(4):481–487. doi: 10.1136/gut.49.4.481 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Harris AG, Hinds FE, Beckhouse AG, Kolesnikow T, Hazell SL (2002) Resistance to hydrogen peroxide in Helicobacter pylori: role of catalase (KatA) and Fur, and functional analysis of a novel gene product designated ‘KatA-associated protein’, KapA (HP0874). Microbiology 148(Pt 12):3813–3825. doi: 10.1099/00221287-148-12-3813 CrossRefPubMedGoogle Scholar
  29. Harris AG, Wilson JE, Danon SJ, Dixon MF, Donegan K, Hazell SL (2003) Catalase (KatA) and KatA-associated protein (KapA) are essential to persistent colonization in the Helicobacter pylori SS1 mouse model. Microbiology 149(Pt 3):665–672. doi: 10.1099/mic.0.26012-0 CrossRefPubMedGoogle Scholar
  30. Hase K, Murakami M, Iimura M, Cole SP, Horibe Y, Ohtake T, Obonyo M, Gallo RL, Eckmann L, Kagnoff MF (2003) Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology 125(6):1613–1625. doi: 10.1053/j.gastro.2003.08.028 CrossRefPubMedGoogle Scholar
  31. Heneghan MA, McCarthy CF, Moran AP (2000) Relationship of blood group determinants on Helicobacter pylori lipopolysaccharide with host lewis phenotype and inflammatory response. Infect Immun 68(2):937–941. doi: 10.1128/IAI.68.2.937-941.2000 CrossRefPubMedPubMedCentralGoogle Scholar
  32. IARC (1994) Infection with Helicobacter pylori. IARC monographs on the evaluation of carcinogenic risks to humans/World Health Organization, International Agency for Research on Cancer 61:177–240Google Scholar
  33. Ishihara S, Rumi MA, Kadowaki Y, Ortega-Cava CF, Yuki T, Yoshino N, Miyaoka Y, Kazumori H, Ishimura N, Amano Y, Kinoshita Y (2004) Essential role of MD-2 in TLR4-dependent signaling during Helicobacter pylori-associated gastritis. J Immunol 173(2):1406–1416. doi: 10.4049/jimmunol.173.2.1406 CrossRefPubMedGoogle Scholar
  34. Kabir S (2011) The role of interleukin-17 in the Helicobacter pylori induced infection and immunity. Helicobacter 16(1):1–8. doi: 10.1111/j.1523-5378.2010.00812.x CrossRefPubMedGoogle Scholar
  35. Kabisch R, Semper RP, Wustner S, Gerhard M, Mejias-Luque R (2016) Helicobacter pylori gamma-glutamyltranspeptidase induces tolerogenic human dendritic cells by activation of glutamate receptors. J Immunol 196(10):4246–4252. doi: 10.4049/jimmunol.1501062 CrossRefPubMedGoogle Scholar
  36. Kaebisch R, Mejias-Luque R, Prinz C, Gerhard M (2014) Helicobacter pylori cytotoxin-associated gene A impairs human dendritic cell maturation and function through IL-10-mediated activation of STAT3. J Immunol 192(1):316–323. doi: 10.4049/jimmunol.1302476 CrossRefPubMedGoogle Scholar
  37. Kao JY, Rathinavelu S, Eaton KA, Bai L, Zavros Y, Takami M, Pierzchala A, Merchant JL (2006) Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense. Am J Physiol Gastrointest Liver Physiol 291(1):G73–G81. doi: 10.1152/ajpgi.00139.2005 CrossRefPubMedGoogle Scholar
  38. Kawahara T, Kohjima M, Kuwano Y, Mino H, Teshima-Kondo S, Takeya R, Tsunawaki S, Wada A, Sumimoto H, Rokutan K (2005) Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells. Am J Physiol Cell Physiol 288(2):C450–C457. doi: 10.1152/ajpcell.00319.2004 CrossRefPubMedGoogle Scholar
  39. Kawauchi K, Yagihashi A, Tsuji N, Uehara N, Furuya D, Kobayashi D, Watanabe N (2006) Human beta-defensin-3 induction in H. pylori-infected gastric mucosal tissues. World J Gastroenterol WJG 12(36):5793–5797. doi: 10.3748/wjg.v12.i36.5793 CrossRefPubMedGoogle Scholar
  40. Khalifeh Gholi M, Kalali B, Formichella L, Gottner G, Shamsipour F, Zarnani AH, Hosseini M, Busch DH, Shirazi MH, Gerhard M (2013) Helicobacter pylori FliD protein is a highly sensitive and specific marker for serologic diagnosis of H. pylori infection. Int J Med Microbiol IJMM 303(8):618–623. doi: 10.1016/j.ijmm.2013.08.005
  41. Kim JM, Kim JS, Yoo DY, Ko SH, Kim N, Kim H, Kim YJ (2011) Stimulation of dendritic cells with Helicobacter pylori vacuolating cytotoxin negatively regulates their maturation via the restoration of E2F1. Clin Exp Immunol 166(1):34–45. doi: 10.1111/j.1365-2249.2011.04447.x CrossRefPubMedPubMedCentralGoogle Scholar
  42. Kraft C, Stack A, Josenhans C, Niehus E, Dietrich G, Correa P, Fox JG, Falush D, Suerbaum S (2006) Genomic changes during chronic Helicobacter pylori infection. J Bacteriol 188(1):249–254. doi: 10.1128/JB.188.1.249-254.2006 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Lebrun AH, Wunder C, Hildebrand J, Churin Y, Zahringer U, Lindner B, Meyer TF, Heinz E, Warnecke D (2006) Cloning of a cholesterol-alpha-glucosyltransferase from Helicobacter pylori. J Biol Chem 281(38):27765–27772. doi: 10.1074/jbc.M603345200 CrossRefPubMedGoogle Scholar
  44. Lewis ND, Asim M, Barry DP, Singh K, de Sablet T, Boucher JL, Gobert AP, Chaturvedi R, Wilson KT (2010) Arginase II restricts host defense to Helicobacter pylori by attenuating inducible nitric oxide synthase translation in macrophages. J Immunol 184(5):2572–2582. doi: 10.4049/jimmunol.0902436 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Ljungh A, Moran AP, Wadstrom T (1996) Interactions of bacterial adhesins with extracellular matrix and plasma proteins: pathogenic implications and therapeutic possibilities. FEMS Immunol Med Microbiol 16(2):117–126. doi: 10.1111/j.1574-695X.1996.tb00128.x CrossRefPubMedGoogle Scholar
  46. Lundgren A, Suri-Payer E, Enarsson K, Svennerholm A-M, Lundin BS (2003) Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infect Immun 71(4):1755–1762. doi: 10.1128/IAI.71.4.1755-1762.2003 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Michel A, Pawlita M, Boeing H, Gissmann L, Waterboer T (2014) Helicobacter pylori antibody patterns in Germany: a cross-sectional population study. Gut Pathog 6:10. doi: 10.1186/1757-4749-6-10 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Miszczyk E, Rudnicka K, Moran AP, Fol M, Kowalewicz-Kulbat M, Druszczynska M, Matusiak A, Walencka M, Rudnicka W, Chmiela M (2012) Interaction of Helicobacter pylori with C-type lectin dendritic cell-specific ICAM grabbing nonintegrin. J Biomed Biotechnol 2012:206463. doi: 10.1155/2012/206463 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Mitchell P, Germain C, Fiori PL, Khamri W, Foster GR, Ghosh S, Lechler RI, Bamford KB, Lombardi G (2007) Chronic exposure to Helicobacter pylori impairs dendritic cell function and inhibits Th1 development. Infect Immun 75(2):810–819. doi: 10.1128/IAI.00228-06 CrossRefPubMedGoogle Scholar
  50. Moran AP (2001) Molecular structure, biosynthesis, and pathogenic roles of lipopolysaccharides. In: Mobley HLT, Mendz GL, Hazell SL (eds) Helicobacter pylori: physiology and genetics. ASM Press, Washington (DC). ISBN-10: 1-55581-213-9Google Scholar
  51. Moran AP (2008) Relevance of fucosylation and Lewis antigen expression in the bacterial gastroduodenal pathogen Helicobacter pylori. Carbohydr Res 343(12):1952–1965. doi: 10.1016/j.carres.2007.12.012 CrossRefPubMedGoogle Scholar
  52. Moran AP, Aspinall GO (1998) Unique structural and biological features of Helicobacter pylori lipopolysaccharides. Prog Clin Biol Res 397:37–49PubMedGoogle Scholar
  53. Muotiala A, Helander IM, Pyhala L, Kosunen TU, Moran AP (1992) Low biological activity of Helicobacter pylori lipopolysaccharide. Infect Immun 60(4):1714–1716 (0019-9567/92/041714-03$02.00/0)Google Scholar
  54. Necchi V, Manca R, Ricci V, Solcia E (2009) Evidence for transepithelial Dcs in human Hp active gastritis. Helicobacter 14:208–222. doi: 10.1111/j.1523-5378.2009.00679.x CrossRefPubMedGoogle Scholar
  55. Nell S, Kennemann L, Schwarz S, Josenhans C, Suerbaum S (2014) Dynamics of Lewis b binding and sequence variation of the babA adhesin gene during chronic Helicobacter pylori infection in humans. MBio 5(6). doi: 10.1128/mBio.02281-14
  56. Nomura AM, Lee J, Stemmermann GN, Nomura RY, Perez-Perez GI, Blaser MJ (2002) Helicobacter pylori CagA seropositivity and gastric carcinoma risk in a Japanese American population. J Infect Dis 186(8):1138–1144. doi: 10.1086/343808 CrossRefPubMedGoogle Scholar
  57. Nuding S, Gersemann M, Hosaka Y, Konietzny S, Schaefer C, Beisner J, Schroeder BO, Ostaff MJ, Saigenji K, Ott G, Schaller M, Stange EF, Wehkamp J (2013) Gastric antimicrobial peptides fail to eradicate Helicobacter pylori infection due to selective induction and resistance. PLoS ONE 8(9):e73867. doi: 10.1371/journal.pone.0073867 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Odenbreit S, Wieland B, Haas R (1996) Cloning and genetic characterization of Helicobacter pylori catalase and construction of a catalase-deficient mutant strain. J Bacteriol 178(23):6960–6967 (0021-9193/96/$04.00)Google Scholar
  59. Oertli M, Noben M, Engler DB, Semper RP, Reuter S, Maxeiner J, Gerhard M, Taube C, Muller A (2013) Helicobacter pylori gamma-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance. Proc Natl Acad Sci USA 110(8):3047–3052. doi: 10.1073/pnas.1211248110 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Oleastro M, Cordeiro R, Menard A, Gomes JP (2010) Allelic diversity among Helicobacter pylori outer membrane protein genes homB and homA generated by recombination. J Bacteriol 192(15):3961–3968. doi: 10.1128/JB.00395-10 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Otani K, Tanigawa T, Watanabe T, Nadatani Y, Sogawa M, Yamagami H, Shiba M, Watanabe K, Tominaga K, Fujiwara Y, Arakawa T (2012) Toll-like receptor 9 signaling has anti-inflammatory effects on the early phase of Helicobacter pylori-induced gastritis. Biochem Biophys Res Commun 426(3):342–349. doi: 10.1016/j.bbrc.2012.08.080 CrossRefPubMedGoogle Scholar
  62. Pachathundikandi SK, Brandt S, Madassery J, Backert S (2011) Induction of TLR-2 and TLR-5 expression by Helicobacter pylori switches cagPAI-dependent signaling leading to the secretion of IL-8 and TNF-α. PLoS ONE 6:e19614. doi: 10.1371/journal.pone.0019614 CrossRefGoogle Scholar
  63. Pachathundikandi SK, Lind J, Tegtmeyer N, El-Omar EM, Backert S (2015) Interplay of the gastric pathogen Helicobacter pylori with toll-like receptors. Biomed Res Int 2015:192420. doi: 10.1155/2015/192420 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Pachathundikandi SK, Müller A, Backert S (2016) Inflammasome activation by Helicobacter pylori and its implications for persistence and immunity. Curr Top Microbiol Immunol 397:117–131. doi: 10.1007/978-3-319-41171-2_6 PubMedGoogle Scholar
  65. Pan KF, Formichella L, Zhang L, Zhang Y, Ma JL, Li ZX, Liu C, Wang YM, Goettner G, Ulm K, Classen M, You WC, Gerhard M (2014) Helicobacter pylori antibody responses and evolution of precancerous gastric lesions in a Chinese population. Int J Cancer 134(9):2118–2125. doi: 10.1002/ijc.28560 CrossRefPubMedGoogle Scholar
  66. Patel SR, Smith K, Letley DP, Cook KW, Memon AA, Ingram RJ, Staples E, Backert S, Zaitoun AM, Atherton JC, Robinson K (2013) Helicobacter pylori downregulates expression of human beta-defensin 1 in the gastric mucosa in a type IV secretion-dependent fashion. Cell Microbiol 15(12):2080–2092. doi: 10.1111/cmi.12174 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Pride DT, Meinersmann RJ, Blaser MJ (2001) Allelic variation within Helicobacter pylori babA and babB. Infect Immun 69(2):1160–1171. doi: 10.1128/IAI.69.2.1160-1171.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Rad R, Ballhorn W, Voland P, Eisenacher K, Mages J, Rad L, Ferstl R, Lang R, Wagner H, Schmid RM, Bauer S, Prinz C, Kirschning CJ, Krug A (2009) Extracellular and intracellular pattern recognition receptors cooperate in the recognition of Helicobacter pylori. Gastroenterology 136(7):2247–2257. doi: 10.1053/j.gastro.2009.02.066 CrossRefPubMedGoogle Scholar
  69. Ramarao N, Meyer TF (2001) Helicobacter pylori resists phagocytosis by macrophages: quantitative assessment by confocal microscopy and fluorescence-activated cell sorting. Infect Immun 69(4):2604–2611. doi: 10.1128/IAI.69.4.2604-2611.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Ramarao N, Gray-Owen SD, Backert S, Meyer TF (2000a) Helicobacter pylori inhibits phagocytosis by professional phagocytes involving type IV secretion components. Mol Microbiol 37(6):1389–1404. doi: 10.1046/j.1365-2958.2000.02089.x CrossRefPubMedGoogle Scholar
  71. Ramarao N, Gray-Owen SD, Meyer TF (2000b) Helicobacter pylori induces but survives the extracellular release of oxygen radicals from professional phagocytes using its catalase activity. Mol Microbiol 38(1):103–113. doi: 10.1046/j.1365-2958.2000.02114.x CrossRefPubMedGoogle Scholar
  72. Rubin EJ, Trent MS (2013) Colonize, evade, flourish: how glyco-conjugates promote virulence of Helicobacter pylori. Gut Microbes 4(6):439–453. doi: 10.4161/gmic.25721 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Sayi A, Kohler E, Hitzler I, Arnold I, Schwendener R, Rehrauer H, Muller A (2009) The CD4+ T cell-mediated IFN-gamma response to Helicobacter infection is essential for clearance and determines gastric cancer risk. J Immunol 182(11):7085–7101. doi: 10.4049/jimmunol.0803293
  74. Schmees C, Prinz C, Treptau T, Rad R, Hengst L, Voland P, Bauer S, Brenner L, Schmid RM, Gerhard M (2007) Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase. Gastroenterology 132(5):1820–1833. doi: 10.1053/j.gastro.2007.02.031 CrossRefPubMedGoogle Scholar
  75. Serelli-Lee V, Ling KL, Ho C, Yeong LH, Lim GK, Ho B, Wong SB (2012) Persistent Helicobacter pylori specific Th17 responses in patients with past H. pylori infection are associated with elevated gastric mucosal IL-1beta. PLoS ONE 7(6):e39199. doi: 10.1371/journal.pone.0039199 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 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 (2008) Integrin subunit CD18 is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin. Cell Host Microbe 3(1):20–29. doi: 10.1016/j.chom.2007.11.003 CrossRefPubMedGoogle Scholar
  77. Sewald X, Jimenez-Soto L, Haas R (2011) PKC-dependent endocytosis of the Helicobacter pylori vacuolating cytotoxin in primary T lymphocytes. Cell Microbiol 13(3):482–496. doi: 10.1111/j.1462-5822.2010.01551.x CrossRefPubMedGoogle Scholar
  78. Seyler RW Jr, Olson JW, Maier RJ (2001) Superoxide dismutase-deficient mutants of Helicobacter pylori are hypersensitive to oxidative stress and defective in host colonization. Infect Immun 69(6):4034–4040. doi: 10.1128/IAI.69.6.4034-4040.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Shi Y, Liu X-F, Zhuang Y, Zhang J-Y, Liu T, Yin Z, Wu C, Mao X-H, Jia K-R, Wang F-J, Guo H, Flavell RA, Zhao Z, Liu K-Y, Xiao B, Guo Y, Zhang W-J, Zhou W-Y, Guo G, Zou Q-M (2010) Helicobacter pylori-induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice. J Immunol 184(9):5121–5129. doi: 10.4049/jimmunol.0901115
  80. Shiota S, Murakami K, Okimoto T, Kodama M, Yamaoka Y (2014) Serum Helicobacter pylori CagA antibody titer as a useful marker for advanced inflammation in the stomach in Japan. J Gastroenterol Hepatol 29(1):67–73. doi: 10.1111/jgh.12359 CrossRefPubMedGoogle Scholar
  81. Smith SM, Moran AP, Duggan SP, Ahmed SE, Mohamed AS, Windle HJ, O’Neill LA, Kelleher DP (2011) Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide. J Immunol 186(4):2462–2471. doi: 10.4049/jimmunol.1000864 CrossRefPubMedGoogle Scholar
  82. Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M (2004) Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci USA 101(7):2106–2111. doi: 10.1073/pnas.0308573100 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Spiegelhalder C, Gerstenecker B, Kersten A, Schiltz E, Kist M (1993) Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene. Infect Immun 61(12):5315–5325 (0019-9567/93/125315-11$02.00/0)Google Scholar
  84. Suerbaum S (2000) Genetic variability within Helicobacter pylori. Int J Med Microbiol IJMM 290(2):175–181. doi: 10.1016/S1438-4221(00)80087-9 CrossRefPubMedGoogle Scholar
  85. Sun X, Zhang M, El-Zataari M, Owyang SY, Eaton KA, Liu M, Chang Y-M, Zou W, Kao JY (2013) TLR2 mediates Helicobacter pylori-induced tolerogenic immune response in mice. PLoS ONE 8(9):e74595. doi: 10.1371/journal.pone.0074595 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Sundrud MS, Torres VJ, Unutmaz D, Cover TL (2004) 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 USA 101(20):7727–7732. doi: 10.1073/pnas.0401528101 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Tanaka H, Yoshida M, Nishiumi S, Ohnishi N, Kobayashi K, Yamamoto K, Fujita T, Hatakeyama M, Azuma T (2010) The CagA protein of Helicobacter pylori suppresses the functions of dendritic cell in mice. Arch Biochem Biophys 498(1):35–42. doi: 10.1016/j.abb.2010.03.021 CrossRefPubMedGoogle Scholar
  88. Tran AX, Whittimore JD, Wyrick PB, McGrath SC, Cotter RJ, Trent MS (2006) The lipid A 1-phosphatase of Helicobacter pylori is required for resistance to the antimicrobial peptide polymyxin. J Bacteriol 188(12):4531–4541. doi: 10.1128/JB.00146-06 CrossRefPubMedPubMedCentralGoogle Scholar
  89. Wang J, Brooks EG, Bamford KB, Denning TL, Pappo J, Ernst PB (2001) Negative selection of T cells by Helicobacter pylori as a model for bacterial strain selection by immune evasion. J Immunol 167(2):926–934. doi: 10.4049/jimmunol.167.2.926 CrossRefPubMedGoogle Scholar
  90. Wehkamp J, Schmidt K, Herrlinger KR, Baxmann S, Behling S, Wohlschlager C, Feller AC, Stange EF, Fellermann K (2003) Defensin pattern in chronic gastritis: HBD-2 is differentially expressed with respect to Helicobacter pylori status. J Clin Pathol 56(5):352–357. doi: 10.1136/jcp.56.5.352 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Whitfield C, Trent MS (2014) Biosynthesis and export of bacterial lipopolysaccharides. Annu Rev Biochem 83:99–128. doi: 10.1146/annurev-biochem-060713-035600 CrossRefPubMedGoogle Scholar
  92. Wroblewski LE, Peek RM, Wilson KT (2010) Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 23(4):713–739. doi: 10.1128/CMR.00011-10 CrossRefPubMedPubMedCentralGoogle Scholar
  93. Wunder C, Churin Y, Winau F, Warnecke D, Vieth M, Lindner B, Zähringer U, Mollenkopf H-J, Heinz E, Meyer TF (2006) Cholesterol glucosylation promotes immune evasion by Helicobacter pylori. Nat Med 12(9):1030–1038. doi: 10.1038/nm1480 CrossRefPubMedGoogle Scholar
  94. Wüstner S, Mejías-Luque R, Koch MF, Rath E, Vieth M, Sieber SA, Haller D, Gerhard M (2015) Helicobacter pylori γ-glutamyltranspeptidase impairs T-lymphocyte function by compromising metabolic adaption through inhibition of cMyc and IRF4 expression. Cell Microbiol 17(1):51–61. doi: 10.1111/cmi.12335 CrossRefPubMedGoogle Scholar
  95. Yokota S, Ohnishi T, Muroi M, Tanamoto K, Fujii N, Amano K (2007) Highly-purified Helicobacter pylori LPS preparations induce weak inflammatory reactions and utilize Toll-like receptor 2 complex but not Toll-like receptor 4 complex. FEMS Immunol Med Microbiol 51(1):140–148. doi: 10.1111/j.1574-695X.2007.00288.x CrossRefPubMedGoogle Scholar
  96. Zabaleta J, McGee DJ, Zea AH, Hernandez CP, Rodriguez PC, Sierra RA, Correa P, Ochoa AC (2004) Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR zeta-chain (CD3zeta). J Immunol 173(1):586–593. doi: 10.4049/jimmunol.173.1.586
  97. Zheng PY, Jones NL (2003) Helicobacter pylori strains expressing the vacuolating cytotoxin interrupt phagosome maturation in macrophages by recruiting and retaining TACO (coronin 1) protein. Cell Microbiol 5(1):25–40. doi: 10.1046/j.1462-5822.2003.00250.x CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institut für Medizinische Mikrobiologie, Immunologie und HygieneTechnische Universität MünchenMunichGermany
  2. 2.German Centre for Infection Research (DZIF), Partner Site MunichMunichGermany

Personalised recommendations