Abstract
The human pathogen Helicobacter pylori interacts intimately with gastric epithelial cells to induce inflammatory responses that are a hallmark of the infection. This inflammation is a critical precursor to the development of peptic ulcer disease and gastric cancer. A major driver of this inflammation is a type IV secretion system (T4SS) encoded by the cag pathogenicity island (cagPAI), present in a subpopulation of more virulent H. pylori strains. The cagPAI T4SS specifically activates signalling pathways in gastric epithelial cells that converge on the transcription factor, nuclear factor-κB (NF-κB), which in turn upregulates key immune and inflammatory genes, resulting in various host responses. It is now clear that H. pylori possesses several mechanisms to activate NF-κB in gastric epithelial cells and, moreover, that multiple signalling pathways are involved in these responses. Two of the dominant signalling pathways implicated in NF-κB-dependent responses in epithelial cells are nucleotide-binding oligomerisation domain 1 (NOD1) and a newly described pathway involving alpha-kinase 1 (ALPK1) and tumour necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain (TIFA). Although the relative roles of these two pathways in regulating NF-κB-dependent responses still need to be clearly defined, it is likely that they work cooperatively and non-redundantly. This chapter will give an overview of the various mechanisms and pathways involved in H. pylori induction of NF-κB-dependent responses in gastric epithelial cells, including a ′state-of-the-art′ review on the respective roles of NOD1 and ALPK1/TIFA pathways in these responses.
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References
Ahmed AU, Sarvestani ST, Gantier MP, Williams BRG, Hannigan GE (2014) Integrin-linked kinase modulates lipopolysaccharide- and Helicobacter pylori-induced nuclear factor κB-activated tumor necrosis factor-α production via regulation of p 65 serine 536 phosphorylation. J Biol Chem 289(40):27776–27793. https://doi.org/10.1074/jbc.M114.574541
Aihara M, Tsuchimoto D, Takizawa H, Azuma A, Wakebe H, Ohmoto Y, Imagawa K Kikuchi M, Mukaida N, Matsushima K (1997) Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. Infect Immun 65(8):3218–3224
Allison CC, Kufer TA, Kremmer E, Kaparakis M, Ferrero RL (2009) Helicobacter pylori induces MAPK phosphorylation and AP-1 activation via a NOD1-dependent mechanism. J Immunol 183(12):8099–8109. https://doi.org/10.4049/jimmunol.0900664
Allison CC, Ferrand J, McLeod L, Hassan M, Kaparakis-Liaskos M, Grubman A, Bhathal PS, Dev A, Sievert W, Jenkins BJ, Ferrero RL (2013) Nucleotide oligomerization domain 1 enhances IFN-γ signaling in gastric epithelial cells during Helicobacter pylori infection and exacerbates disease severity. J Immunol 190(7):3706–3715. https://doi.org/10.4049/jimmunol.1200591
Alvi A, Ansari SA, Ehtesham NZ, Rizwan M, Devi S, Sechi LA, Qureshi IA, Hasnain SE, Ahmed N (2011) Concurrent proinflammatory and apoptotic activity of a Helicobacter pylori protein (HP986) points to its role in chronic persistence. PLoS One. 6(7):e22530. https://doi.org/10.1371/journal.pone.0022530
Asano N, Imatani A, Watanabe T, Fushiya J, Kondo Y, Jin X, Ara N, Uno K, Iijima K, Koike T, Strober W, Shimosegawa T (2016) Cdx2 expression and intestinal metaplasia induced by H. pylori infection of gastric cells is regulated by NOD1-mediated innate immune responses. Cancer Res 76(5):1135–1145. https://doi.org/10.1158/0008-5472.CAN-15-2272
Backert S, Naumann M (2010) What a disorder: proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiol 18(11):479–486. https://doi.org/10.1016/j.tim.2010.08.003
Backert S, Ziska E, Brinkmann V, Zimny-Arndt U, Fauconnier A, Jungblut PR, Naumann M, Meyer TF (2000) Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell Microbiol 2(2):155–164. https://doi.org/10.1046/j.1462-5822.2000.00043.x
Backert S, Feller SM, Wessler S (2008) Emerging roles of Abl family tyrosine kinases in microbial pathogenesis. Trends Biochem Sci 33(2):80–90. https://doi.org/10.1016/j.tibs.2007.10.006
Backert S, Tegtmeyer N, Fischer W (2015) Composition, structure and function of the Helicobacter pylori cag pathogenicity island encoded type IV secretion system. Future Microbiol 10:955–965
Bodger K, Bromelow K, Wyatt JI, Heatley RV (2001) Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion. J Clin Pathol 54(4):285–292. https://doi.org/10.1136/JCP.54.4.285
Boonyanugomol W, Chomvarin C, Hahnvajanawong C, Sripa B, Kaparakis-Liaskos M, Ferrero RL (2013) Helicobacter pylori cag pathogenicity island (cagPAI) involved in bacterial internalization and IL-8 induced responses via NOD1- and MyD88-dependent mechanisms in human biliary epithelial cells. PLoS ONE 8(10):e77358. https://doi.org/10.1371/journal.pone.0077358
Boughan PK, Argent RH, Body-Malapel M, Park J-H, Ewings KE, Bowie AG, Ong SJ, Cook SJ, Sorensen OE, Manzo BA, Inohara N, Klein NJ, Nuñez G, Atherton JC, Bajaj-Elliott M (2006) Nucleotide-binding oligomerization domain-1 and epidermal growth factor receptor. J Biol Chem 281(17):11637–11648. https://doi.org/10.1074/jbc.M510275200
Brandt S, Kwok T, Hartig R, König W, Backert S (2005) NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci U S A 102(26):9300–9305. https://doi.org/10.1073/pnas.0409873102
Caruso R, Fina D, Peluso I, Fantini MC, Tosti C, Del Vecchio Blanco G, Paoluzi OA, Caprioli F, Andrei F, Stolfi C, Romano M, Ricci V, MacDonald TT, Pallone F, Monteleone G (2007) IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. J Immunol 178(9):5957–5965. https://doi.org/10.4049/jimmunol.178.9.5957
Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A (1996) cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A 93(25):14648–14653. https://doi.org/10.1073/PNAS.93.25.14648
Chen GY, Shaw MH, Redondo G, Nunez G (2008) The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. Cancer Res 68(24):10060–10067. https://doi.org/10.1158/0008-5472.CAN-08-2061
Cook KW, Letley DP, Ingram RJM, Staples E, Skjoldmose H, Atherton JC, Robinson K (2014) CCL20/CCR6-mediated migration of regulatory T cells to the Helicobacter pylori-infected human gastric mucosa. Gut 63(10):1550–1559. https://doi.org/10.1136/gutjnl-2013-306253
Crabtree JE, Xiang Z, Lindley IJ, Tompkins DS, Rappuoli R, Covacci A (1995) Induction of interleukin-8 secretion from gastric epithelial cells by a cagA negative isogenic mutant of Helicobacter pylori. J Clin Pathol 48(10):967–969. https://doi.org/10.1136/jcp.48.10.967
da Silva Correia J, Miranda Y, Austin-Brown N, Hsu J, Mathison J, Xiang R, Zhou H, Li Q, Han J, Ulevitch RJ (2006) Nod1-dependent control of tumor growth. Proc Natl Acad Sci 103(6):1840–1845. https://doi.org/10.1073/pnas.0509228103
da Silva Correia J, Miranda Y, Leonard N, Hsu J, Ulevitch RJ (2007) Regulation of Nod1-mediated signaling pathways. Cell Death Differ 14(4):830–839. https://doi.org/10.1038/sj.cdd.4402070
El-Omar EM, Chow W, Rabkin CS (2001) Gastric cancer and H. pylori: host genetics open the way. Gastroenterology 121(4):1002–1004. https://doi.org/10.1053/gast.2001.28739
Fernandez-Gonzalez E, Backert S (2014) DNA transfer in the gastric pathogen Helicobacter pylori. J Gastroenterol 49(4):594–604. https://doi.org/10.1007/s00535-014-0938-y
Ferrero RL, Ave P, Ndiaye D, Bambou J-C, Huerre MR, Philpott DJ, Memet S (2008) NF-kappaB activation during acute Helicobacter pylori infection in mice. Infect Immun 76(2):551–561. https://doi.org/10.1128/IAI.01107-07
Fischer W, Püls J, Buhrdorf R, Gebert B, Odenbreit S, Haas R (2001) Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol Microbiol 42(5):1337–1348. https://doi.org/10.1046/j.1365-2958.2001.02714.x
Fritz JH, Le Bourhis L, Sellge G, Magalhaes JG, Fsihi H, Kufer TA, Collins C, Viala J, Ferrero RL, Girardin SE, Philpott DJ (2007) Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity. Immunity 26(4):445–459. https://doi.org/10.1016/j.immuni.2007.03.009
Fukazawa A, Alonso C, Kurachi K, Gupta S, Lesser CF, McCormick BA, Reinecker H-C (2008) GEF-H1 mediated control of NOD1 dependent NF-κB activation by Shigella effectors. PLoS Pathog 4(11):e1000228. https://doi.org/10.1371/journal.ppat.1000228
Gall A, Gaudet RG, Gray-Owen SD, Salama NR (2017) TIFA signaling in gastric epithelial cells initiates the cag type 4 secretion system-dependent innate immune response to Helicobacter pylori infection. MBio 8(4):e01168–17. https://doi.org/10.1128/mBio.01168-17
Gaudet RG, Sintsova A, Buckwalter CM, Leung N, Cochrane A, Li J, Cox AD, Moffat J, Gray-Owen SD (2015) Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity. Science 348(6240):1251–1255. https://doi.org/10.1126/science.aaa4921
Girardin SE, Tournebize R, Mavris M, Page A-L, Li X, Stark GR, Bertin J, DiStefano PS, Yaniv M, Sansonetti PJ, Philpott DJ (2001) CARD4/Nod1 mediates NF-κB and JNK activation by invasive Shigella flexneri. EMBO Rep 2(8):736–742. https://doi.org/10.1093/embo-reports/kve155
Glocker E, Lange C, Covacci A, Bereswill S, Kist M, Pahl HL (1998) Proteins encoded by the cag pathogenicity island of Helicobacter pylori are required for NF-kappaB activation. Infect Immun 66(5):2346–2348
Gobert AP, Bambou JC, Werts C, Balloy V, Chignard M, Moran AP, Ferrero RL (2004) Helicobacter pylori heat shock protein 60 mediates interleukin-6 production by macrophages via a toll-like receptor (TLR)-2-, TLR-4-, and myeloid differentiation factor 88-independent mechanism. J Biol Chem 279(1):245–250
Gööz M, Shaker M, Gööz P, Smolka AJ (2003) Interleukin 1beta induces gastric epithelial cell matrix metalloproteinase secretion and activation during Helicobacter pylori infection. Gut 52(9):1250–1256. https://doi.org/10.1136/gut.52.9.1250
Gorrell RJ, Guan J, Xin Y, Tafreshi MA, Hutton ML, McGuckin MA, Ferrero RL, Kwok T (2013) A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system. Cell Microbiol 15(4):554–570. https://doi.org/10.1111/cmi.12055
Grubman A, Kaparakis M, Viala J, Allison C, Badea L, Karrar A, Boneca IG, Le Bourhis L, Reeve S, Smith IA, Hartland EL, Philpott DJ, Ferrero RL (2010) The innate immune molecule, NOD1, regulates direct killing of Helicobacter pylori by antimicrobial peptides. Cell Microbiol 12(5):626–639. https://doi.org/10.1111/j.1462-5822.2009.01421.x
Hammond CE, Beeson C, Suarez G, Peek RM, Backert S, Smolka AJ, Smolka AJ (2015) Helicobacter pylori virulence factors affecting gastric proton pump expression and acid secretion. Am J Physiol Gastrointest Liver Physiol 309(3):G193–G201. https://doi.org/10.1152/ajpgi.00099.2015
Hirata Y, Maeda S, Ohmae T, Shibata W, Yanai A, Ogura K, Yoshida H, Kawabe T, Omata M (2006a) Helicobacter pylori induces IkappaB kinase alpha nuclear translocation and chemokine production in gastric epithelial cells. Infect Immun 74(3):1452–1461. https://doi.org/10.1128/IAI.74.3.1452-1461.2006
Hirata Y, Ohmae T, Shibata W, Maeda S, Ogura K, Yoshida H, Kawabe T, Omata M (2006b) MyD88 and TNF receptor-associated factor 6 are critical signal transducers in Helicobacter pylori-infected human epithelial cells. J Immunol 176(6):3796–3803. https://doi.org/10.4049/JIMMUNOL.176.6.3796
Hornsby MJ, Huff JL, Kays RJ, Canfield DR, Bevins CL, Solnick JV (2008) Helicobacter pylori induces an antimicrobial response in rhesus macaques in a cag pathogenicity island-dependent manner. Gastroenterology 134(4):1049–1057. https://doi.org/10.1053/j.gastro.2008.01.018
Huang FY, Chan AOO, Rashid A, Wong DKH, Cho CH, Yuen MF (2012) Helicobacter pylori induces promoter methylation of E-cadherin via interleukin-1β activation of nitric oxide production in gastric cancer cells. Cancer 118(20):4969–4980. https://doi.org/10.1002/cncr.27519
Hutton ML, Kaparakis-Liaskos M, Turner L, Cardona A, Kwok T, Ferrero RL (2010) Helicobacter pylori exploits cholesterol-rich microdomains for induction of NF-kappaB-dependent responses and peptidoglycan delivery in epithelial cells. Infect Immun 78(11):4523–4531. https://doi.org/10.1128/IAI.00439-10
Irving AT, Mimuro H, Kufer TA, Lo C, Wheeler R, Turner LJ, Thomas BJ, Malosse C, Gantier MP, Casillas LN, Votta BJ, Bertin J, Boneca IG, Sasakawa C, Philpott DJ, Ferrero RL, Kaparakis-Liaskos M (2014) The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling. Cell Host Microbe 15(5):623–635. https://doi.org/10.1016/j.chom.2014.04.001
Isomoto H, Miyazaki M, Mizuta Y, Takeshima F, Murase K, Inoue K, Yamasaki K, Murata I, Koji T, Kohno S (2000) Expression of nuclear factor-kappaB in Helicobacter pylori-infected gastric mucosa detected with southwestern histochemistry. Scand J Gastroenterol 35(3):247–254. https://doi.org/10.1080/003655200750024092
Jiménez-Soto LF, Kutter S, Sewald X, Ertl C, Weiss E, Kapp U, Rohde M, Pirch T, Jung K, Retta SF, Terradot L, Fischer W, Haas R (2009) Helicobacter pylori type IV secretion apparatus exploits beta1 integrin in a novel RGD-independent manner. PLoS Pathog 5(12):e1000684. https://doi.org/10.1371/journal.ppat.1000684
Kaparakis M, Turnbull L, Carneiro L, Firth S, Coleman HA, Parkington HC, Le Bourhis L, Karrar A, Viala J, Mak J, Hutton ML, Davies JK, Crack PJ, Hertzog PJ, Philpott DJ, Girardin SE, Whitchurch CB, Ferrero RL (2010) Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol 12(3):372–385. https://doi.org/10.1111/j.1462-5822.2009.01404.x
Keates S, Hitti YS, Upton M, Kelly CP (1997) Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells. Gastroenterology 113(4):1099–1109. https://doi.org/10.1053/gast.1997.v113.pm9322504
Kim EJ, Lee JR, Chung WC, Jung SH, Sung HJ, Lee YW, Oh YS, Kim SB, Paik CN, Lee K-M, Noh SJ (2013) Association between genetic polymorphisms of NOD1 and Helicobacter pylori-induced gastric mucosal inflammation in healthy Korean population. Helicobacter 18(2):143–150. https://doi.org/10.1111/hel.12020
Kim BJ, Kim JY, Hwang ES, Kim JG (2015) Nucleotide binding oligomerization domain 1 is an essential signal transducer in human epithelial cells infected with Helicobacter pylori that induces the transepithelial migration of neutrophils. Gut Liver 9(3):358–369. https://doi.org/10.5009/gnl13218
Kudo T, Lu H, Wu J, Ohno T, Wu MJ, Genta RM, Graham DY, Yamaoka Y (2007) Pattern of transcription factor activation in Helicobacter pylori–infected Mongolian gerbils. Gastroenterology 132(3):1024–1038. https://doi.org/10.1053/j.gastro.2007.01.009
Kupcinskas J, Wex T, Bornschein J, Selgrad M, Leja M, Juozaityte E, Kiudelis G, Jonaitis L, Malfertheiner P (2011) Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians. BMC Med Genet 12(1):112. https://doi.org/10.1186/1471-2350-12-112
Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, König W, Backert S (2007) Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449(7164):862–866. https://doi.org/10.1038/nature06187
Lamb A, Yang XD, Tsang YHN, Li JD, Higashi H, Hatakeyama M, Peek RM, Blanke SR, Chen LF (2009) Helicobacter pylori CagA activates NF-kappaB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination. EMBO Rep 10(11):1242–1249. https://doi.org/10.1038/embor.2009.210
Lin Q, Xu H, Xi Chen, Tang G, Gu L, Wang Y (2015) Helicobacter pylori cytotoxin-associated gene A activates tumor necrosis factor-α and interleukin-6 in gastric epithelial cells through P300/CBP-associated factor-mediated nuclear factor-κB p65 acetylation. Mol Med Rep 12(4):6337–6345. https://doi.org/10.3892/mmr.2015.4143
Lina TT, Alzahrani S, House J, Yamaoka Y, Sharpe AH, Rampy BA, Pinchuk IV, Reyes VE (2015) Helicobacter pylori cag pathogenicity island’s role in B7-H1 induction and immune evasion. PLoS ONE 10(3):e0121841. https://doi.org/10.1371/journal.pone.0121841
Liu W, Yan M, Liu Y, Wang R, Li C, Deng C, Singh A, Coleman WG, Rodgers GP (2010) Olfactomedin 4 down-regulates innate immunity against Helicobacter pylori infection. Proc Natl Acad Sci 107(24):11056–11061. https://doi.org/10.1073/pnas.1001269107
Lu H, Wu JY, Kudo T, Ohno T, Graham DY, Yamaoka Y (2005) Regulation of interleukin-6 promoter activation in gastric epithelial cells infected with Helicobacter pylori. Mol Biol Cell 16(10):4954–4966. https://doi.org/10.1091/mbc.e05-05-0426
Ma B, Hua K, Zhou S, Zhou H, Chen Y, Luo R, Bi D, Zhou R, He Q, Jin H (2018) Haemophilus parasuis infection activates NOD1/2-RIP2 signaling pathway in PK-15 cells. Dev Comp Immunol 79:158–165. https://doi.org/10.1016/j.dci.2017.10.021
Maeda S, Akanuma M, Mitsuno Y, Hirata Y, Ogura K, Yoshida H, Shiratori Y, Omata M (2001) Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells. J Biol Chem 276(48):44856–44864. https://doi.org/10.1074/jbc.M105381200
Mandell L, Moran AP, Cocchiarella A, Houghton J, Taylor N, Fox JG, Wang TC, Kurt-Jones EA (2004) Intact gram-negative Helicobacter pylori, Helicobacter felis, and Helicobacter hepaticus bacteria activate innate immunity via toll-like receptor 2 but not toll-like receptor 4. Infect Immun 72(11):6446–6454. https://doi.org/10.1128/IAI.72.11.6446-6454.2004
Merino E, Flores-Encarnación M, Aguilar-Gutiérrez GR (2017) Functional interaction and structural characteristics of unique components of Helicobacter pylori T4SS. FEBS J 284(21):3540–3549. https://doi.org/10.1111/febs.14092
Milivojevic M, Dangeard A-S, Kasper CA, Tschon T, Emmenlauer M, Pique C, Schnupf P, Guignot J, Arrieumerlou C (2017) ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-bisphosphate of gram-negative bacteria. PLoS Pathog 13(2):e1006224. https://doi.org/10.1371/journal.ppat.1006224
Münzenmaier A, Lange C, Glocker E, Covacci A, Moran A, Bereswill S, Baeuerle PA, Kist M, Pahl HL (1997) A secreted/shed product of Helicobacter pylori activates transcription factor nuclear factor-kappa B. J Immunol 159(12):6140–6147
Murray PJ (2005) NOD proteins: an intracellular pathogen-recognition system or signal transduction modifiers? Curr Opin Immunol 17(4):352–358. https://doi.org/10.1016/j.coi.2005.05.006
Odenbreit S, Püls J, Sedlmaier B, Gerland E, Fischer W, Haas R (2000) Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287(5457):1497–1500. https://doi.org/10.1126/science.287.5457.1497
Ohmae T, Hirata Y, Maeda S, Shibata W, Yanai A, Ogura K, Yoshida H, Kawabe T, Omata M (2005) Helicobacter pylori activates NF-kappaB via the alternative pathway in B lymphocytes. J Immunol 175(11):7162–7169. https://doi.org/10.4049/JIMMUNOL.175.11.7162
Olbermann P, Josenhans C, Moodley Y, Uhr M, Stamer C, Vauterin M, Suerbaum S, Achtman M, Linz B (2010) A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PLoS Genet 6(8):e1001069. https://doi.org/10.1371/journal.pgen.1001069
Opitz B, Förster S, Hocke AC, Maass M, Schmeck B, Hippenstiel S, Suttorp N, Krüll M (2005) Nod1-mediated endothelial cell activation by Chlamydophila pneumoniae. Circ Res 96(3):319–326. https://doi.org/10.1161/01.RES.0000155721.83594.2c
Pachathundikandi K, Backert S (2018) Heptose 1,7-Bisphosphate directed TIFA oligomerization: a novel PAMP-recognizing signaling platform in the control of bacterial infections. Gastroenterology 154:778–783. https://doi.org/10.1053/j.gastro.2018.01.009
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108. https://doi.org/10.3322/canjclin.55.2.74
Patel SR, Smith K, Letley DP, Cook KW, Memon AA, Ingram RJM, Staples E, Backert S, Zaitoun AM, Atherton JC, Robinson K (2013) Helicobacter pylori downregulates expression of human β-defensin 1 in the gastric mucosa in a type IV secretion-dependent fashion. Cell Microbiol 15(12):2080–2092. https://doi.org/10.1111/cmi.12174
Rieder G, Einsiedl W, Hatz RA, Stolte M, Enders GA, Walz A (2001) Comparison of CXC chemokines ENA-78 and interleukin-8 expression in Helicobacter pylori-associated gastritis. Infect Immun 69(1):81–88. https://doi.org/10.1128/IAI.69.1.81-88.2001
Rosenstiel P, Hellmig S, Hampe J, Ott S, Till A, Fischbach W, Sahly H, Lucius R, Folsch UR, Philpott D, Schreiber S (2006) Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. Cell Microbiol 8(7):1188–1198. https://doi.org/10.1111/j.1462-5822.2006.00701.x
Saha A, Hammond CE, Beeson C, Peek RM, Smolka AJ, Smolka AJ (2010) Helicobacter pylori represses proton pump expression and inhibits acid secretion in human gastric mucosa. Gut 59(7):874–881. https://doi.org/10.1136/gut.2009.194795
Salama NR, Hartung ML, Müller A (2013) Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol 11(6):385–399. https://doi.org/10.1038/nrmicro3016
Segal ED, Falkow S, Tompkins LS (1996) Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins. Proc Natl Acad Sci U S A 93(3):1259–1264. https://doi.org/10.1073/pnas.93.3.1259
Segal ED, Cha J, Lo J, Falkow S, Tompkins LS (1999) Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc Natl Acad Sci U S A 96(25):14559–14564. https://doi.org/10.1073/pnas.96.25.14559
Sharma SA, Tummuru MK, Blaser MJ, Kerr LD (1998) Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-kappa B in gastric epithelial cells. J Immunol 160(5):2401–2407
Shibata W, Hirata Y, Yoshida H, Otsuka M, Hoshida Y, Ogura K, Maeda S, Ohmae T, Yanai A, Mitsuno Y, Seki N, Kawabe T, Omata M (2005) NF-kappaB and ERK-signaling pathways contribute to the gene expression induced by cag PAI-positive-Helicobacter pylori infection. World J Gastroenterol 11(39):6134–6143. https://doi.org/10.3748/WJG.V11.I39.6134
Shin S, Case CL, Archer KA, Nogueira CV, Kobayashi KS, Flavell RA, Roy CR, Zamboni DS (2008) Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila. PLoS Pathog 4(11):e1000220. https://doi.org/10.1371/journal.ppat.1000220
Sokolova O, Maubach G, Naumann M (2014) MEKK3 and TAK1 synergize to activate IKK complex in Helicobacter pylori infection. Biochim Biophys Acta—Mol Cell Res 1843(4):715–724. https://doi.org/10.1016/j.bbamcr.2014.01.006
Sorbara MT, Philpott DJ (2011) Peptidoglycan: a critical activator of the mammalian immune system during infection and homeostasis. Immunol Rev 243(1):40–60. https://doi.org/10.1111/j.1600-065X.2011.01047.x
Stein M, Rappuoli R, Covacci A (2000) Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A 97(3):1263–1268. https://doi.org/10.1073/pnas.97.3.1263
Stein SC, Faber E, Bats SH, Murillo T, Speidel Y, Coombs N, Josenhans C (2017) Helicobacter pylori modulates host cell responses by CagT4SS-dependent translocation of an intermediate metabolite of LPS inner core heptose biosynthesis. PLoS Pathog 13(7):e1006514. https://doi.org/10.1371/journal.ppat.1006514
Strober W, Murray PJ, Kitani A, Watanabe T (2006) Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol 6(1):9–20. https://doi.org/10.1038/nri1747
Suarez G, Romero-Gallo J, Piazuelo MB, Wang G, Maier RJ, Forsberg LS, Azadi P, Gomez MA, Correa P, Peek RM (2015) Modification of Helicobacter pylori peptidoglycan enhances NOD1 activation and promotes cancer of the stomach. Cancer Res 75(8):1749–1759. https://doi.org/10.1158/0008-5472.CAN-14-2291
Tan X, Wei LJ, Fan GJ, Jiang YN, Yu XP (2015) Effector responses of bovine blood neutrophils against Escherichia coli: Role of NOD1/NF-κB signalling pathway. Vet Immunol Immunopathol 168(1–2):68–76. https://doi.org/10.1016/j.vetimm.2015.08.010
Tanahashi T, Kita M, Kodama T, Yamaoka Y, Sawai N, Ohno T, Mitsufuji S, Wei YP, Kashima K, Imanishi J (2000) Cytokine expression and production by purified Helicobacter pylori urease in human gastric epithelial cells. Infect Immun 68(2):664–671. https://doi.org/10.1128/IAI.68.2.664-671.2000
Tegtmeyer N, Neddermann M, Asche CI, Backert S (2017) Subversion of host kinases: a key network in cellular signaling hijacked by Helicobacter pylori CagA. Mol Microbiol 105:358–372. https://doi.org/10.1111/mmi.13707
Tran LS, Tran D, De Paoli A, D’Costa K, Creed SJ, Ng GZ, Le L, Sutton P, Silke J, Nachbur U, Ferrero RL (2018) NOD1 is required for Helicobacter pylori induction of IL-33 responses in gastric epithelial cells. Cell Microbiol 20(5):e12826. https://doi.org/10.1111/cmi.12826
Tummuru MK, Cover TL, Blaser MJ (1993) Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun 61(5):1799–1809
van Den Brink GR, ten Kate FJ, Ponsioen CY, Rive MM, Tytgat GN, van Deventer SJ, Peppelenbosch MP (2000) Expression and activation of NF-kappa B in the antrum of the human stomach. J Immunol 164(6):3353–3359. https://doi.org/10.4049/jimmunol.164.6.3353
Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Mémet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL (2004) Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5(11):1166–1174. https://doi.org/10.1038/ni1131
Wang P, Zhang L, Jiang J-M, Ma D, Tao H-X, Yuan S-L, Wang Y-C, Wang L-C, Liang H, Zhang Z-S, Liu C-J (2012) Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population. World J Gastroenterol 18(17):2112. https://doi.org/10.3748/wjg.v18.i17.2112
Watanabe T, Asano N, Fichtner-Feigl S, Gorelick PL, Tsuji Y, Matsumoto Y, Chiba T, Fuss IJ, Kitani A, Strober W (2010a) NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway. J Clin Invest 120(5):1645–1662. https://doi.org/10.1172/JCI39481
Watanabe T, Asano N, Kitani A, Fuss IJ, Chiba T, Strober W (2010b) NOD1-mediated mucosal host defense against Helicobacter pylori. Int J Inflam 2010:1–6. https://doi.org/10.4061/2010/476482
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. https://doi.org/10.1111/j.1574-695X.2007.00288.x
Zhan Y, Seregin SS, Chen J, Chen GY (2016) Nod1 limits colitis-associated tumorigenesis by regulating IFN-γ production. J Immunol 196(12):5121–5129. https://doi.org/10.4049/jimmunol.1501822
Zhang XS, Tegtmeyer N, Traube L, Jindal S, Perez-Perez G, Sticht H, Backert S, Blaser MJ (2015) A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interaction. PloS Pathog 11:e1004621. https://doi.org/10.1371/journal.ppat.1004621
Zhao Q, Busch B, Jiménez-Soto LF, Ishikawa-Ankerhold H, Massberg S, Terradot L, Fischer W, Haas R, Blanke SR (2018) Integrin but not CEACAM receptors are dispensable for Helicobacter pylori CagA translocation. PLOS Pathogens 14(10):e1007359. https://doi.org/10.1371/journal.ppat.1007359
Zhou P, She Y, Dong N, Li P, He H, Borio A, Wu Q, Lu S, Ding X, Cao Y, Xu Y, Gao W, Dong M, Ding J, Wang D-C, Zamyatina A, Shao F (2018) Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. Nature 561(7721):122–126. https://doi.org/10.1038/s41586-018-0433-3
Zimmermann S, Pfannkuch L, Al-Zeer MA, Bartfeld S, Koch M, Liu J, Rechner C, Soerensen M, Sokolova O, Zamyatina A, Kosma P, Mäurer AP, Glowinski F, Pleissner K-P, Schmid M, Brinkmann V, Karlas A, Naumann M, Rother M, Machuy N, Meyer TF (2017) ALPK1- and TIFA-dependent innate immune response triggered by the Helicobacter pylori type IV secretion system. Cell Rep 20(10):2384–2395. https://doi.org/10.1016/j.celrep.2017.08.039
Acknowledgements
The authors thank Christian Ferrero for the preparation of Fig. 1. Research in RLF’s laboratory is supported by a project grant (APP1107930) and a Senior Research Fellowship (APP1079904) from the National Health and Medical Research Council of Australia. Dr. L. Ying’s position is supported by funding from the U. S. Department of Defense (Award No. W81XWH-17-1-0606). Research at the Hudson Institute of Medical Research is supported by the Victorian Government’s Operational Infrastructure Support Program.
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Ying, L., Ferrero, R.L. (2019). Role of NOD1 and ALPK1/TIFA Signalling in Innate Immunity Against Helicobacter pylori Infection. In: Backert, S. (eds) Molecular Mechanisms of Inflammation: Induction, Resolution and Escape by Helicobacter pylori. Current Topics in Microbiology and Immunology, vol 421. Springer, Cham. https://doi.org/10.1007/978-3-030-15138-6_7
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