Advertisement

Role of NOD1 and ALPK1/TIFA Signalling in Innate Immunity Against Helicobacter pylori Infection

  • Le Ying
  • Richard L. FerreroEmail author
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 421)

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.

Keywords

NOD1 TIFA ALPK1 Peptidoglycan cagPAI 

Notes

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.

References

  1. 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
  2. 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):3218–3224Google Scholar
  3. 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.0900664CrossRefPubMedGoogle Scholar
  4. 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.1200591CrossRefPubMedGoogle Scholar
  5. 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
  6. 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
  7. 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.2010.08.003CrossRefPubMedGoogle Scholar
  8. 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.xCrossRefPubMedGoogle Scholar
  9. 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
  10. 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 10:955–965CrossRefGoogle Scholar
  11. 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.54.4.285CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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.0077358CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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.M510275200CrossRefPubMedGoogle Scholar
  14. 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.0409873102CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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.178.9.5957CrossRefPubMedGoogle Scholar
  16. 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.93.25.14648CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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-08-2061CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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-2013-306253CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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.48.10.967CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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.0509228103CrossRefGoogle Scholar
  21. 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.4402070CrossRefGoogle Scholar
  22. 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
  23. 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-yCrossRefPubMedGoogle Scholar
  24. 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.01107-07CrossRefPubMedGoogle Scholar
  25. 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.xCrossRefPubMedGoogle Scholar
  26. 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.2007.03.009CrossRefGoogle Scholar
  27. 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.1000228CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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
  29. 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.aaa4921CrossRefPubMedGoogle Scholar
  30. 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/kve155CrossRefPubMedPubMedCentralGoogle Scholar
  31. 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):2346–2348PubMedPubMedCentralGoogle Scholar
  32. 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):245–250Google Scholar
  33. 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.52.9.1250CrossRefPubMedPubMedCentralGoogle Scholar
  34. 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.12055CrossRefPubMedGoogle Scholar
  35. 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.xCrossRefPubMedGoogle Scholar
  36. 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.00099.2015CrossRefPubMedPubMedCentralGoogle Scholar
  37. 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.74.3.1452-1461.2006CrossRefPubMedPubMedCentralGoogle Scholar
  38. 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.176.6.3796CrossRefPubMedGoogle Scholar
  39. 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.2008.01.018CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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.27519CrossRefPubMedGoogle Scholar
  41. 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.00439-10CrossRefPubMedPubMedCentralGoogle Scholar
  42. 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.2014.04.001CrossRefPubMedGoogle Scholar
  43. 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/10.1080/003655200750024092CrossRefPubMedGoogle Scholar
  44. 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
  45. 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.xCrossRefPubMedGoogle Scholar
  46. 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.pm9322504CrossRefPubMedGoogle Scholar
  47. 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.12020CrossRefPubMedGoogle Scholar
  48. 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/gnl13218CrossRefPubMedGoogle Scholar
  49. 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.2007.01.009CrossRefPubMedPubMedCentralGoogle Scholar
  50. 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/10.1186/1471-2350-12-112CrossRefPubMedPubMedCentralGoogle Scholar
  51. 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/nature06187CrossRefPubMedGoogle Scholar
  52. 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.2009.210CrossRefPubMedPubMedCentralGoogle Scholar
  53. 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.2015.4143CrossRefPubMedGoogle Scholar
  54. 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.0121841CrossRefPubMedPubMedCentralGoogle Scholar
  55. 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.1001269107CrossRefPubMedGoogle Scholar
  56. 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.e05-05-0426CrossRefPubMedPubMedCentralGoogle Scholar
  57. 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.2017.10.021CrossRefPubMedGoogle Scholar
  58. 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.M105381200CrossRefPubMedGoogle Scholar
  59. 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
  60. 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.14092CrossRefPubMedGoogle Scholar
  61. 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.1006224CrossRefPubMedPubMedCentralGoogle Scholar
  62. 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):6140–6147PubMedGoogle Scholar
  63. 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.2005.05.006CrossRefPubMedGoogle Scholar
  64. 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.287.5457.1497CrossRefPubMedGoogle Scholar
  65. 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.175.11.7162CrossRefPubMedGoogle Scholar
  66. 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.1001069CrossRefPubMedPubMedCentralGoogle Scholar
  67. 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.0000155721.83594.2cCrossRefPubMedGoogle Scholar
  68. 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.2018.01.009CrossRefPubMedGoogle Scholar
  69. 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.55.2.74CrossRefGoogle Scholar
  70. 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.12174CrossRefPubMedPubMedCentralGoogle Scholar
  71. 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.69.1.81-88.2001CrossRefPubMedPubMedCentralGoogle Scholar
  72. 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.xCrossRefPubMedGoogle Scholar
  73. 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.2009.194795CrossRefPubMedPubMedCentralGoogle Scholar
  74. 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/nrmicro3016CrossRefPubMedPubMedCentralGoogle Scholar
  75. 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.93.3.1259CrossRefPubMedPubMedCentralGoogle Scholar
  76. 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.96.25.14559CrossRefPubMedPubMedCentralGoogle Scholar
  77. 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):2401–2407PubMedGoogle Scholar
  78. 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.I39.6134CrossRefPubMedPubMedCentralGoogle Scholar
  79. 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.1000220CrossRefPubMedPubMedCentralGoogle Scholar
  80. 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
  81. 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.xCrossRefPubMedGoogle Scholar
  82. 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.97.3.1263CrossRefPubMedPubMedCentralGoogle Scholar
  83. 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.1006514CrossRefPubMedPubMedCentralGoogle Scholar
  84. 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/nri1747CrossRefPubMedGoogle Scholar
  85. 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-14-2291CrossRefPubMedPubMedCentralGoogle Scholar
  86. 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.2015.08.010CrossRefPubMedGoogle Scholar
  87. 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.68.2.664-671.2000CrossRefPubMedPubMedCentralGoogle Scholar
  88. 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.13707CrossRefPubMedGoogle Scholar
  89. 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.12826CrossRefPubMedGoogle Scholar
  90. 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):1799–1809PubMedPubMedCentralGoogle Scholar
  91. 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.164.6.3353CrossRefGoogle Scholar
  92. 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/ni1131CrossRefPubMedGoogle Scholar
  93. 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.i17.2112CrossRefPubMedPubMedCentralGoogle Scholar
  94. 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/JCI39481CrossRefPubMedPubMedCentralGoogle Scholar
  95. 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/10.4061/2010/476482CrossRefGoogle Scholar
  96. 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.xCrossRefPubMedGoogle Scholar
  97. 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.1501822CrossRefPubMedPubMedCentralGoogle Scholar
  98. 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
  99. 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
  100. 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/s41586-018-0433-3CrossRefPubMedGoogle Scholar
  101. 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.2017.08.039CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical ResearchMonash UniversityClaytonAustralia
  2. 2.Department of Molecular and Translational MedicineMonash UniversityClaytonAustralia
  3. 3.Department of Microbiology, Biomedicine Discovery InstituteMonash UniversityClaytonAustralia

Personalised recommendations