Significance of pathogenicity factors in initiation of immune response in Helicobacter pylori infection

Cover Page

Cite item

Full Text

Abstract

Helicobacter pylori is a unique microorganism capable of long-term colonization of the gastric mucosa, induction of the inflammatory process, antigenic mimicry and immune evasia. Flagella proteins, adhesins, invasive and aggressive enzymes, cytotoxin-associated protein, vacuolating cytotoxin can have a damaging effect on stomach epithelial cells. Recognition of molecular patterns of Helicobacter pylori by stomach cell receptors initiates activation of adapter proteins, protein kinases and transcription factors, leading to the production of proinflammatory cytokines, infiltration by neutrophilic granulocytes, absorption and killing of microorganisms by phagocytes with presentation of antigens to lymphocytes, while the activity and completeness of phagocytosis remain at a low level. Activation of CD8+-, CD16+- lymphocytes is accompanied by cytotoxic effect on both Helicobacter pylori and epithelial cells of the gastric mucosa. Weak immunogenicity of Helicobacter pylori antigens limits the production of anti-Helicobacter antibodies. Thus, activation of immune factors, in most cases, does not lead to complete elimination of the pathogen, but can aggravate the pathomorphological changes of the gastric epithelium.

About the authors

L. V. Matveeva

National Research Ogarev Mordovia State University

Author for correspondence.
Email: MatveevaLjubov1@mail.ru
Saransk, Russian Federation

R. H. Kapkaeva

National Research Ogarev Mordovia State University

Email: MatveevaLjubov1@mail.ru
Saransk, Russian Federation

A. N. Chudajkin

National Research Ogarev Mordovia State University

Email: MatveevaLjubov1@mail.ru
Saransk, Russian Federation

L. V. Novikova

National Research Ogarev Mordovia State University

Email: MatveevaLjubov1@mail.ru
Saransk, Russian Federation

References

  1. Pozdeev O.K., Pozdeeva A.O., Valeeva Yu.V., Gulyaev P.E. Mechanisms of interraction of Helicobacter pylori with epithelium of gastric mucosa. I. Pathogenic factors promoting successful colonization. Russian Journal of Infection and Immunity = Infektsiya i immunitet. 2018. 8(3): 273—83. doi: 10.15789/2220—7619—2018—3— 273—283
  2. Gu H. Role of Flagella in the Pathogenesis of Helicobacter pylori. Current Microbiology. 2017. 74(7):863—9. doi: 10.1007/s00284—017—1256—4
  3. Radin J.N., Gaddy J.A., González-Rivera C., Loh J.T., Scott Algood H.M., Cover T.L. Flagellar Localization of a Helicobacter pylori Autotransporter Protein. mBio. 2013. 4(2): e00613—12. https://doi.org/10.1128/mBio.00613—12
  4. Schkitin V.A., Schpirna A.I., Starovoytov G.N. Role of Helicobacter pylori in Human Pathology. Clinical Microbiology and Antimicrobial Chemotherapy. 2002. 4(2): 128—45.
  5. Backert S., Clyne M., Tegtmeyer N. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori. Cell Commun. Signal. 2011. 9: 28. doi: 10.1186/1478—811X-9—28
  6. Carlsohn E., Nystrom J., Bolin I., Nilsson C.L., Svennerholm A.M. HpaA is essential for Helicobacter pylori colonization in mice. Infect. Immun. 2006. Vol. (2): 920—6. doi: 10.1128/IAI.74.2.920—926.2006
  7. Joo J.S., Park K.C., Song J.Y., Kim D.H., Lee K.J., Kwon Y.C., et al. A thin-layer liquid culture technique for the growth of Helicobacter pylori. Helicobacter. 2010. 15. (4): 295—302. doi: 10.1111/j.1523—5378.2010.00767.x
  8. Mine T., Muraoka H., Saika T., Kobayashi I. Characteristics of a clinical isolate of ureasenegative Helicobacter pylori and its ability to induce gastric ulcers in Mongolian gerbils. Helicobacter. 2005. Vol. 10(2):125—31. doi: 10.1111/j.1523—5378.2005.00300.x
  9. Celli J.P., Turner B.S., Afdhal N.H., Keates S., Ghiran I., Kelly C.P., et al. Helicobacter pylori moves through mucus by reducing mucin viscoelasticity. Proc. Natl. Acad. Sci. USA. 2009. 106. (34): 14321–.6. doi: 10.1073/ pnas.0903438106
  10. Celli J.P., Turner B.S., Afdhal N.H., Ewoldt R.H., McKinley G.H., Bansil R., et al. Rheology of gastric mucin exhibits a pH-dependent sol-gel transition. Biomacromolecules. 2007. 8(5): 1580—6. doi: 10.1021/bm0609691
  11. Yokota S., Amano K., Hayashi S., Kubota T., Fujii N., Yokochi T. Human antibody response to Helicobacter pylori lipopolysaccharide: presence of an immunodominant epitope in the polysaccharide chain of lipopolysaccharide. Infect. Immun. 1998. 66(6): 3006—11.
  12. Bäckhed F., Rokbi B., Torstensson E., Zhao Y., Nilsson C, Seguin D., et al. Gastric mucosal recognition of Helicobacter pylori is independent of Toll-like receptor 4. J. Infect. Dis. 2003. 187(5): 829—36. doi: 10.1086/367896
  13. De Jonge R., Durrani Z., Rijpkema S.G., Kuipers E.J., Van Vliet A.H.M., Kusters J.G. Role of the Helicobacter pylori outermembrane proteins AlpA and AlpB in colonization of the guinea pig stomach. J. Med. Microbiol. 2004. 53 (5): 375—79. doi: 10.1099/jmm.0.45551—0
  14. Yamaoka Y., Kikuchi S., El Zimaity H.M., Gutierrez O., Osato M.S., Graham D.Y. Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology. 2002. 123(2): 414—24. doi: 10.1053/gast.2002.34781
  15. Tabassam F.H., Graham D.Y., Yamaoka Y. OipA plays a role in Helicobacter pylori-induced focal adhesion kinase activation and cytoskeletal reorganization. Cell. Microbiol. 2008. 10(4): 1008—20. doi: 10.1111/j.1462— 5822.2007.01104.x
  16. Kido M., Watanabe N., Aoki N., Iwamoto S., Nishiura H., Maruoka R., et al. Dual roles of CagA protein in Helicobacter pylori-induced chronic gastritis in mice. Biochem. Biophys. Res. Commun. 2011. 412(2): 266—272. doi: 10.1016/j.bbrc.2011.07.081
  17. Mahla R.S., Reddy M.C., Prasad D.V., Kumar H. Sweeten PAMPs: role of sugar complexed PAMPs in innate immunity and vaccine biology. Frontiers in Immunology. 2013. 4: 248.
  18. Matveeva L.V. Mechanisms of cellular cytotoxicity induction in gastric mucosal inflammation. Medical Immunology (Russia)/Meditsinskaya Immunologiya. 2017. (6): 673—682. doi: 10.15789/1563—0625—2017— 6—673—682
  19. Viala J., Chaput C., Boneca I.G., Cardona A., Girardin S.E., Moran A.P., et al. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat. Immunol. 2004. 5(11): 1166—74. doi: 10.1038/ni1131
  20. Amedei A., Cappon A., Codolo G., Cabrelle A., Polenghi A., Benagiano M., et al. The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses. J. Clin. Invest. 2006. 116. 4: 1092—1101. doi: 10.1172/JCI27177
  21. Morozov I.A. Helicobacter pylori and inflammatory processes in the stomach. Almanac of clinical medicine. 2006. 14: 72—8.
  22. Ricci V., Sommi P., Romano M. The vacuolating toxin of Helicobacter pylori: a few answers, many questions. Digest. Liver Dis. 2000. 32. Suppl. 3. P. S178–S181. doi: 10.1016/S1590—8658(00)80271—6
  23. Cover T.L., Blanke S.R. Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat. Rev. Microbiol. 2005. 3(4):320—32. doi: 10.1038/nrmicro1095
  24. Gong M., Ling S.S., Lui S.Y., Yeoh K.G., Ho B. Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology. 2010. 139(2): 564—73. doi: 10.1053/j.gastro.2010.03.050
  25. Oertli M., Noben M., Engler D.B., Semper R.P., Reuter S., Maxeiner J., et al. Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance. Proc. Natl. Acad. Sci. USA. 2013.110(8): 3047—52. doi: 10.1073/ pnas.1211248110
  26. Tang R.X., Luo D.J., Sun A.H., Yan J. Diversity of Helicobacter pylori isolates in expression of antibodies // World J. Gastroenterol. 2008. 14(30): 4816—22. doi: 10.3748/wjg.14.4816
  27. Pohl M.A., Romero-Gallo J., Guruge J.L., Tse D.B., Gordon J.I., Blaser M.J. Host-dependent Lewis (Le) antigen expression in Helicobacter pylori cells recovered from Leb-transgenic mice. J. Exp. Med. 2009.206(3):3061—72. doi: 10.1084/jem.20090683
  28. Monteiro M.A., St Michael F., Rasko D.A., Taylor D.E., Conlan J.W., Chan K.H., et al. Helicobacter pylori from asymptomatic hosts expressing heptoglycan but lacking Lewis O-chains: Lewis blood-group O-chains may play a role in Helicobacter pylori induced pathology. Biochem. Cell. Biol. 2001. 79(4): 449—59. doi: 10.1139/bcb-79— 4—449
  29. Moran A.P. Relevance of fucosylation and Lewis antigen expression in the bacterial gastroduodenal pathogen Helicobacter pylori. Carbohydr. Res. 2008. 343(12): 1952—65. doi: 10.1016/j.carres.2007.12.012
  30. Wessler S., Backert S. Molecular mechanisms of epithelialbarrier disruption by Helicobacter pylori. Trends Microbiol. 2008. 16(8): 397—405. doi: 10.1016/j.tim.2008.05.005
  31. Iunusova A.I., Litvinova I.S., Karpenok P.A., Tohidpour A. The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor. J. Sib. Fed. Univ. Biol. 2018. 11(1):4—15. doi: 10.17516/1997—1389—0015.
  32. Hosoda K., Shimomura H., Hayashi S, Yokota K., Hirai Y. Steroid hormones as bactericidal agents to Helicobacter pylori. FEMS microbiology letters. 2011. 318(1): 68—75. doi: 10.1111/j.1574—6968.2011.02239.x
  33. Lindgren A., Pavlovic V., Flach C.F., Sjöling A., Lundin S. Interferon-gamma secretion is induced in IL-12 stimulated human NK cells by recognition of Helicobacter pylori or TLR2 ligands. Innate Immunity. 2011.17 (2):191—203. doi: 10.1177/1753425909357970
  34. Rieder G., Fischer W., Haas R. Interaction of Helicobacter pylori with host cells: function of secreted and translocated molecules. Cur. Opin. Microbiol. 2005. 8(1):67—73. doi: 10.1016/j.mib.2004.12.004
  35. De Bernard M., D’Elios M.M. The immune modulating activity of the Helicobacter pylori HP-NAP: Friend or foe? Toxicon. 2010. 56 (7): 1186—11. doi: 10.1016/j. toxicon.2009.09.020
  36. Kim I.J., Blanke S.R. Remodeling the host environment: modulation of the gastric epithelium by the Helicobacter pylori vacuolating toxin (VacA). Front. Cell. Infect. Microbiol. 2012. 2: 37—40. doi: 10.3389/ fcimb.2012.00037
  37. Kronsteiner B., Bassaganya-Riera J., Philipson N., Hontecillas R. Novel insights on the role of CD8+T cells and cytotoxic responses during Helicobacter pylori infection. Gut Microbes. 2014. 5 (3): 357—62. doi: 10.4161/gmic.28899
  38. Bagheri N., Shirzad H., Elahi S., Azadegan-Dehkordi F., Rahimian G., Shafigh M., et al. Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection. Microbial Pathogenesis. 2017. 6:165—75. doi: 10.1016/j.micpath.2017.06.040
  39. Azem J., Svennerholm A.M., Lundin B.S. B cells pulsed with Helicobacter pylori antigen efficiently activate memory CD8+T cells from H. pylori-infected individuals. Clinical Immunology. 2006.118: 284—91. doi: 10.1016/j. clim.2005.09.011
  40. Ohtani N., Ohtani H., Nakayama T., Naganuma H., Sato E., Imai T., et al. Infiltration of CD8+T cells containing RANTES/CCL5+cytoplasmic granules in actively inflammatory lesions of human chronic gastritis. Laboratory investigation. 2004. 84(3): 368—75. doi: 10.1038/labinvest.3700039

Copyright (c) 2020 Matveeva L.V., Kapkaeva R.H., Chudajkin A.N., Novikova L.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies