Журнал МедиАль. 2019; : 55-69
Особенности иммунного ответа человека на инфицирование Helicobacter pylori
https://doi.org/10.21145/2225-0026-2019-2-55-69Аннотация
Helicobacter pylori считается этиологическим агентом острых и хронических форм гастрита, а также способен оказывать многофакторное воздействие на организм хозяина и на характер иммунного ответа. Воспалительная реакция на инфекцирование H. pylori имеет свои особенности. При активном течении воспалительных реакций, когда ослабевает модулирующее действие регуляторных Т-лимфоцитов (T-reg) и активируются популяции провоспалительных клеток (Т-хелперы 1-, 17-, 22-го типов и фолликулярные Т-хелперы), возникают выраженные деструктивные изменения слизистой желудка и двенадцатиперстной кишки. Макрофаги, дендритные клетки и нейтрофилы являются клеточными факторами врожденной иммунной системы и так же, как и адаптивный иммунитет, обеспечивают защиту от инфекции. В свою очередь H. pylori использует разнообразные механизмы ухода от уничтожения иммунной системы хозяина. Длительное сохранение воспаления может вызвать локальную активизацию мутагенеза, инициирующую развитие злокачественных новообразований слизистой желудка. Рассмотрению особенностей иммунного ответа организма-хозяина на H. pylori посвящен настоящий аналитический обзор.
Конфликт интересов. Авторы заявляют об отсутствии явного или потенциального конфликта интересов, связанного с публикацией статьи.
Список литературы
1. Chen Y., Blaser M.J. Helicobacter pylori colonization is inversely associated with childhood asthma. J. Infect. Dis. 2008. Vol. 198. P. 553–560.
2. Lerner A., Arleevskaya M., Schmiedl A. et al. Microbes and viruses are bugging the gut in celiac disease. Are they friends or foes? Front. Microbiol. 2017. Vol. 8. P. 1392.
3. Хомерики С.Г. Helicobacter pylori индуктор и эффектор окислительного стресса в слизистой оболочке желудка: традиционные представления и новые данные. Экспериментальная и клиническая гастроэнтерология. 2006. № 1. C. 37–46.
4. Ильчишина Т.А. Особенности лабораторной диагностики Helicobacter pylori и клинического течения хронического гастрита и язвенной болезни при бациллярно-кокковом дисморфизме бактерии^ Автореф. диcс. ... канд. мед. наук. СПб., 2008. C. 23.
5. Исаков В.А., Домрадский И.В. Хеликобактериоз. М.: Медпрактика, 2003. С. 412.
6. Lu H., Yamaoka Y., Graham D.Y. Helicobacter pylori virulence factors: facts and fantasies. Curr. Opin. Gastroenterol. 2005. Vol. 21. P. 653–659.
7. Shiota. S., Suzuki R., Yamaoka Y. The significance of virulence factors in Helicobacter pylori. J. of digestive diseases. 2013. Vol. 14. №. 3. P. 341–349.
8. Bell G.D. Clinical practice breath tests. Br Med Bull. 1998. Vol. 54. P. 187–193.
9. Tang R.X., Luo D.J., Sun A.H., Yan J. Diversity of Helicobacter pylori isolates in expression of antigens and induction of antibodies. World J Gastroenterol. 2008. Vol. 14. № 30. P. 4816-4822.
10. Исаева Г.Ш., Валиева Р.И. Биологические свойства и вирулентность Helicobacter pylori. Минздрав России, Казань, Россия. 2018. Т. 20. № 1. С. 14-20.
11. Чернявский В.И., Бирюкова С.В. и др. Helicobacter pylori-Herpesviridae ассоциации в этиопатогенезе неопластических поражений желудка, современные аспекты изучения. Анали. Мечниковського Iнституту. 2005. № 1. С. 48–62.
12. Low H.H., Gubellini F., Rivera-Calzada A. et al. Structure of a type IV secretion system. Nature. 2014. Vol. 10. Р. 1038–1043.
13. Solnick J.V., Hansen L.M., Salama N.R., et al. Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc. Natl. Acad. Sci. USA. 2004. Vol. 101. P. 2106–2111.
14. Маев И.В., Самсонов А.А., Андреев Д.Н. Инфекция Helicobacter pylori. М.: ГЭОТАР-Медиа, 2016. C. 256.
15. Yamaoka Y., Kita M., Kodama T., et al. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive 500 Helicobacter pylori strains. Gut 1997. Vol. 41. P. 442–45
16. Dadashzadeh K. Milani M., Somi M.H. The prevalence of Helicobacter pylori CagA and IceA genotypes and possible clinical outcomes. Acta. Medica. mediterranea. 2015. Vol. 31. P. 1345–1349.
17. Aziz F., Chen X., Yang X., Yan Q. Prevalence and correlation with clinical diseases of Helicobacter pylori cagA and vacA genotype among gastric patients from Northeast China. BioMed research international. 2014. Vol. 1. P. 201–2010.
18. Барышникова Н.В. Актуальные проблемы диагностики хеликобактериоза. Экспериментальная и клиническая гастроэнтерология. 2009. № 2. С. 50–58.
19. Перфилова К.М., Неумоиной Н.В., Неумоиной М.В., и др. Генетические маркеры Н.pylori при хеликобактер-ассоциированных заболеваниях. Аналитический обзор. Нижний Новгород: ФБУН ННИИЭМ им.академика И.Н.Блохиной Роспотребнадзора, 2016. 38 с.
20. Hase K., Murakami M., Iimura M., et al. Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology. 2003. Vol. 125. № 6. P. 1613-1625.
21. Schmausser B., Andrulis M., Endrich S. et al. Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and TLR9 on the gastric epithelium in Helicobacter pylori infection. Clin. Exp. Immunol. 2004. Vol. 136. P. 521–526.
22. D’Elios M.M., Andersen L.P. Inflammation, immunity, and vaccines for Helicobacter pylori. Helicobacter. 2009. Vol. 14. P. 21–28.
23. Izcue A, Coombes JL, Powrie F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol Rev. 2006. Vol. 212. P. 256–271.
24. Kaparakis M., Philpott D.J, Ferrero R.L. Mammalian NLR proteins; discriminating foe from friend. Immunol Cell Biol. 2007. P. 495–502.
25. Чернуцкая С.П. Гервазиева В.Б. Роль иммунной системы в персистенции Helicobacter pylori. Инфекционные болезни. 2008. T. 6. № 2. C. 69–77.
26. Birkholz S., Schneider T., Knipp U., et al. Decreased Helicobacter pylorispecific gastric secretory IgA antibodies in infected patients. Digestion. 1998. Vol. 59. № 6. P. 638–645.
27. Gorrell R.J., Wijburg O.L., Pedersen J.S. et al. Contribution of secretory antibodies to intestinal mucosal immunity against Helicobacter pylori. Infect Immun. 2013. Vol. 81. № 10. P. 3880–3893.
28. Кононов А.В. Местный иммунный ответ на инфекцию Helicobacter pylori. Рос. журн. гастроэнтерол., гепатол., колопроктол. 1999. T. 2. C. 15–21.
29. Liutu M., Kalimo K., Uksila J., Savolainen J. Extraction of IgE-binding components of Helicobacter pylori by immunoblotting analysis in chronic urticaria patients. Int.Arch. Allergy Immunol. 2001. Vol. 126. № 3. P. 213–217.
30. Мазурина С.А., Ильинцева Н.В., Агафонов В.Е., Гервазиева В.Б. Антихеликобактерные IgE антитела у детей с заболеваниями гастродуоденальной зоны и сопутствующей аллергопатологией. Экспериментальная и клиническая гастроэнтерология. 2013. № 9. P. 21–25.
31. Berczi L., Sebestyen A., Fekete B., et al. IgE-containing cells in gastric mucosa with and without Helicobacter pylori infection.Pathol. Res. Pract. 2000. Vol. 196. № 12. P. 831–834.
32. Мазурина С.А., Ильинцева Н.В. и др. Иммунный ответ слизистой оболочки желудка на инфицирование Helicobacter pylori у детей, страдающих гастродуоденальной патологией и аллергией. Клиническая гастроэнтерология | clinical gastroenterology. 2014. Т. 109. № 9. С. 30-34.
33. Дубцова Е.А. Некоторые иммунологические аспекты язвообразования. Экспериментальная и клиническая гастроэнтерология. 2002. Т. 4. C. 9–14.
34. Чернин В.В. Язвенная болезнь, хронический гастрит и эзофагит в аспекте дисбактериоза эзофагогастродуоденальной зоны. Экспериментальная и клиническая гастроэнтерология. 2008. T. 3. C. 68–69.
35. Morris A.J., Ali M.R., Nicholson G.I. et al. Long-term follow up of voluntary ingestion of Helicobacter pylori. Ann. Intern. Med. 1991. Vol. 114. P. 662–663.
36. Nurgalieva Z.Z., Conner M.E., Opekun A.R. et al. B-cell and T-cell immune responses to experimental Helicobacter pylori infection in humans. Infect. Immun. 2005. Vol. 73. C. 2999–3006.
37. Warren J.R. Gastric pathology associated with Helicobacter pylori. Gastroenterol. Clin. North. Am. 2000. Vol. 29. P. 705-751.
38. Lundgren A., Stromberg E., Sjoling A. et al. Mucosal FOXP3-expressing CD4+CD25high regulatory T cells in Helicobacter pylori-infected patients. Infect. Immun. 2005. Vol. 73. C. 523–531.
39. Lee S.K., Stack A., Katzowitsch E. et al. Helicobacter pylori flagellins have very low intrinsic activity to stimulate human gastric epithelial cells via TLR5. Microbes Infect. 2003. Vol. 5. P. 1345–1356.
40. Makristathis A., Rokita E., Labigne A. et al. Highly significant role of Helicobacter pylori urease in phagocytosis and production of oxygen metabolites by human granulocytes. J Infect Dis. 1998. Vol. 177. P. 803–806.
41. Dubois A., Born T. Helicobacter pylori is invasive and it may be a facultative intracellular organism. Cell. Microbiol. 2007. Vol. 9. P. 1108–1116.
42. Fehlings M., Drobbe L., Moos V. et al. Comparative analysis of the interaction of Helicobacter pylori with human dendritic cells, macrophages, and monocytes. Infect. Immun. 2012. Vol. 80. P. 2724–2734.
43. Gobert A.P., Bambou J.C., Werts C. et al. 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. 2004. Vol. 279. P. 245–250.
44. Zheng P.Y., Jones N.L. Helicobacter pylori strains expressing the vacuolating cytotoxin interrupt phagosome maturation in macrophages by recruiting and retaining TACO (coronin 1) protein. Cell Microbiol. 2003. Vol. 5. P. 25–40.
45. Allen L.A., Allgood J.A. Atypical protein kinase C-zeta is essential for delayed phagocytosis of Helicobacter pylori. Curr. Biol. 2002. Vol. 12. P. 1762–1766.
46. Wang Y.H., Wu J.J., Lei H.Y. When Helicobacter pylori invades and replicates in the cells. Autophagy. 2009. Vol. 5. P. 540–542.
47. Rittig M.G., Shaw. B., Letley D.P. et al. Helicobacter pylori-induced homotypic phagosome fusion in human monocytes is independent of the bacterial vacA and cag status. Cell. Microbiol. 2003. Vol. 5. P. 887–899.
48. Schwartz J.T., Allen L.A. Role of urease in megasome formation and Helicobacter pylori survival in macrophages. J. Leukoc. Biol. 2006. Vol. 79. P. 1214–1225.
49. Menaker R.J., Ceponis P.J., Jones N.L. Helicobacter pylori induces apoptosis of macrophages in association with alterations in the mitochondrial pathway. Infect. Immun. 2004. Vol. 72. P. 2889–2898.
50. Basu M., Czinn S.J., Blanchard T.G. Absence of catalase reduces long-term survival of Helicobacter pylori in macrophage phagosomes. Helicobacter. 2004. Vol. 9. P. 211–216.
51. Satin B., Giuseppe del Giudice, Della Bianca V., et al. The Neutropil-activating Protein (HP-NAP) of Helicobacter pylori Is a Protective Antigen and a Major Virulence Factor. J. of Experimental Medicine. 2000. Vol. 191. P. 1467–1476.
52. Schmausser B., Josenhans C., Endrich S., et al. Downregulation of CXCR1 and CXCR2 expression on human neutrophils by Helicobacter pylori: a new pathomechanism in H. pylori infection? Infect. Immun. 2004. Vol. 72. P. 6773–6779.
53. Mahnke K., Ring S., Johnson T.S., Schallenberg S., Schоnfeld K., Storn V., Bedke T., Enk A.H. Induction of immunosuppressive functions of dendritic cells in vivo by CD4+CD25+ regulatory T cells: Role of B7-H3 expression and antigen presentation. Eur. J. Immunol. 2007. Vol. 37. P. 2117–2126.
54. Necchi V., Manca R., Ricci V., Solcia E. Evidence for transepithelial dendritic cells in human H. pylori active gastritis. Helicobacter. 2009. Vol. 14. P. 208–222.
55. Mitchell P., Germain C., Fiori P.L., Khamri W., Foster G.R., Ghosh S., et al. Chronic exposure to Helicobacter pylori impairs dendritic cell function and inhibits Th1 development. Infect. Immun. 2007. Vol. 75. P. 810–819.
56. Bergman M.P., Engering A., Smits H. H., et al. Helicobacter pylori modulates the T helpercell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J. Exp. Med. 2004. Vol. 200. P. 979–990.
57. Ieni A., Barresi V., Rigoli L., et al. Morphological and Cellular Features of Innate Immune Reaction in Helicobacter pylori Gastritis: A Brief Review. Int. J. Mol. Sci. 2016. Vol. 17. P. 109.
58. Bagheri N., Azadegan-Dehkordi F., Rahimian G., Rafieian-Kopaei M., Shirzad H. Role of regulatory T-cells in different clinical expressions of Helicobacter pylori infection. Arch Med Res. 2016. Vol. 47. P. 245–254.
59. Razavi A., Bagheri N., Azadegan-Dehkordi F., Shirzad M., Rahimian G., Rafieian-Kopaei M., et al. Comparative Immune Response in Children and Adults with H. pylori Infection. J. Immunol. Res. 2015. Vol. 2015. P. 315957.
60. Bagheri N., Salimzadeh L., Shirzad H. The role of T helper 1-cell response in Helicobacter pylori-infection. Microbial Pathogenesis. 2018. Vol. 123. P. 1–8.
61. Del Giudice G., Covacci A., Telford J.L., Montecucco C., Rappuoli R. The design of vaccines against Helicobacter pylori and their development. Annu. Rev. Immunol. 2001. Vol.19. P. 523–563.
62. Bimczok D., Clements R.H., Waites K.B., Novak L., Eckhoff D.E., Mannon P.J., et al. Human primary gastric dendritic cells induce a Th1 response to H. pylori. Mucosal Immunol. 2010. Vol. 3. P. 260–269.
63. Tourani M., Habibzadeh M., Karkhah A., Shokri-Shirvani J., Barari L., Nouri H.R. Association of TNFalpha but not IL-1beta levels with the presence of Helicobacter pylori infection increased the risk of peptic ulcer development. Cytokine. 2018. Vol. 110. P. 232–236
64. Freire de Melo F., Rocha G.A., Rocha A.M., Teixeira K.N., Pedroso S.H., Pereira Junior J.B., et al. Th1 immune response to H. pylori infection varies according to the age of the patients and influences the gastric inflammatory patterns. Int. J. Med. Microbiol. 2014. Vol. 304. P. 300–306.
65. Annunziato F., Romagnani S. The transient nature of the Th17 phenotype. Eur. J. Immunol. 2010. Vol. 40. P. 3312–3316.
66. Acosta-Rodriguez E.V., Rivino L., Geginat J. et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T-helper memory cells. Nat. Immunol. 2007. Vol. 8. P. 639–646.
67. Adamsson J., Ottsjo L.S., Lundin S.B., Svennerholm A.M., Raghavan S. Gastric expression of IL-17A and IFNgamma in Helicobacter pylori infected individuals is related to symptoms. Cytokine. 2017. Vol. 99. P. 30–34.
68. Yokota K., Kobayashi K., Kawahara Y., Hayashi S., Hirai Y., Mizuno M., et al. Gastric ulcers in SCID mice induced by Helicobacter pylori infection after transplanting lymphocytes from patients with gastric lymphoma. Gastroenterology. 1999. Vol. 117. P. 893–899.
69. 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. Vol. 110. P. 165–175.
70. Матвеичев А.В., Талаев В.Ю., Евплова И.А. физиология и функционирование T-хелперов 17-го типа. Успехи современной биологии. 2016. Т. 136. № 3. С. 285–300.
71. Caruso F. Pallone, Monteleone G. Emerging role of IL-23/IL-17 axis in Helicobacter pylori-associated pathology. J Gastroenterol. 2007. Vol. 14. P. 5547–5551. 7
72. Luzza F., Parrello T., Monteleone G. et al. Up-Regulation of IL-17 Is Associated with Bioactive IL-8 Expression in Helicobacter pylori-Infected Human Gastric Mucosa. J. of Immun. 2019. Vol. 165. P. 5332–5337.
73. Pappu R., Rutz S., Ouyang W. Regulation of epithelial immunity by IL-17 family cytokines. Trends Immunol. 2012. Vol. 33. P. 343–349.
74. Ayraud S., Janvier B., Fauchere J.L. Experimental colonization of mice by fresh clinical isolates of Helicobacter pylori is not influenced by the cagA status and the vacA genotype. FEMS Immunol. Med Microbiol. 2002. Vol. 34. P. 169–172.
75. Jadidi-Niaragh F., Mirshafiey A. Th17 сell, the new player of neuroinflammatory process in multiple sclerosis. Scand. J. Immunol. 2011. Vol. 74. P. 1–13.
76. Martin B., Hirota K., Cua D.J. et al. Interleukin-17-producing T cells selectively expand in response to pathogen products and environmental signals. Immunity. 2009. Vol. 31. P. 321–330.
77. Tanaka S., Nagashima H., Cruz M. et al. Interleukin-17C in human Helicobacter pylori gastritis. Infect Immun. 2017. Vol. 85. P. 389-417.
78. Yamaoka Y., Kita M., Kodama T. et al. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive 500 Helicobacter pylori strains. Gut 1997. Vol. 41. P. 442–45
79. Gu C., Wu L., Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013. Vol. 64. P. 477–485.
80. Song X, Gao H, Lin Y. et al. Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. Immunity. 2014. Vol. 40. P. 140–152.
81. Uhlen M., Oksvold P., Fagerberg L. et al. Towards a knowledge-based Human Protein Atlas. Nat Biotech 2010. Vol. 28. P. 1248–1250.
82. Shi Y., Liu X.F., Zhuang Y., Zhang J.Y., Liu T., Yin Z. et al. Helicobacter pylori induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice. J. Immunol. 2010. Vol. 184. P. 5121–5129.
83. Цыганова М.И., Талаева М.В., Талаев В.Ю. и др. Влияние Helicobacter pylori на содержание провоспалительных Т-клеточных цитокинов и продуцирующих их субпопуляций. Анализ риска здоровью. 2018. № 3. С. 120–127.
84. Конорев М.Р. Иммунный ответ при персистенции Н.Pylori на слизистых оболочках с желудочным эпителием. Иммунопатология, аллергология, инфектология. 2010. № 2. C. 55–62.
85. Leber A., Abedi V., Hontecillas R. et al. Bistability analyses of CD4+ T follicular helper and regulatory cells during Helicobacter pylori infection. J Theor Biol. 2016. Vol. 398. P. 74–84.
86. Талаева М.В., Талаев В.Ю. Воронина Е.В. и др. Экспрессия хемокиновых рецепторов на Т-хелперах крови при заболеваниях, ассоциированных с H. pylori. Х Всероссийская научно-практическая конференция молодых ученых и специалистов Роспотребнадзора «Современные проблемы эпидемиологии, микробиологии и гигиены». 2018. С. 275–279.
87. Zavros Y., Rathinavelu S., Kao J.Y. et al. Treatment of Helicobacter gastritis with IL-4 requires somatostatin. Proc. Natl. Acad. Sci. USA. 2003. Vol. 100. P. 12944–12949.
88. Ceponis P.J., McKay D.M., Menaker R.J. et al. Helicobacter pylori infection interferes with epithelial Stat6-mediated interleukin-4 signal transduction independent of cagA, cagE, or VacA. J. Immunol. 2003. Vol. 171. P. 2035–2041.
89. Watanabe K., Murakami K., Sato R. et al. CTLA-4 blockade inhibits induction of Helicobacter pylori-associated gastritis in mice. Clin. Exp. Immunol. 2004. Vol. 135. P. 29–34.
90. Ismail H.F., Zhang J., Lynch R.G. et al. Role for complement in development of Helicobacter-induced gastritis in interleukin-10-deficient mice. Infect. Immun. 2003. Vol. 71. P. 7140–7148.
91. Rad R., Brenner L., Bauer S., Schwendy S., Layland L., da Costa C.P. et al. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology. 2006. Vol. 131. P. 525–537.
92. Jang T.J. The number of Foxp3-positive regulatory T cells is increased in Helicobacter pylori gastritis and gastric cancer. Pathol Res Pract. 2010. Vol. 206. P. 34–38.
93. Sun X., Zhang M., El-Zaatari M., Huffnagle G.B., Kao J.Y. CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis. Helicobacter. 2016. P. 1–9.
94. Guiney D.G., Hasegawa P., Cole S.P. Helicobacter pylori preferentially induces interleukin 12 (IL-12) rather than IL-6 or IL-10 in human dendritic cells. Infect. Immun. 2003. Vol. 710. P. 4163–4166.
95. Hoffman P.S., Vats N., Hutchison D. et al. Development of an interleukin-12 deficient mouse model that is permissive for colonization by a motile KE26695 strain of Helicobacter pylori. Infect. Immun. 2003. Vol. 71. P. 2534–2541.
96. Holck S., Norgaard A., Bennedsen M. et al. Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacteria load. FEMS Immunol. Med. Microbiol. 2003. Vol. 36. P. 175–180.
97. Матвеичев А.В., Талаева М.В., Талаев В.Ю. Влияние Helicobacter pylori на дифференцировку Т-регуляторных клеток. Анализ риска здоровью. 2017. № 1. С. 21–28.
98. Jafarzadeh A., Larussa T., Nemati M., Jalapour S. T cell subsets play an important role in the determination of the clinical outcome of Helicobacter pylori infection. Microb Pathog. 2018. Vol. 116. P. 227–236.
99. Bagheri N., Azadegan-Dehkordi F., Shirzad H/ et al. (2015) The biological functions of IL-17 in different clinical expressions of Helicobacter pyloriinfection. Microb. Pathog. 2015. Vol. 81. P. 33–38.
100. Wan Y. Multi-tasking of helper T cells.Immunology 2010. Vol. 130. P. 166–171.
101. Zhuang Y. A pro-inflammatory role for Th22 cells in Helicobacter pyloriassociated gastritis. Gut. 2014. P. 1368–1378.
102. Shamsdin S.A., Alborzi A., Rasouli M. et al. Alterations in Th17 and the respective cytokine levels in Helicobacter pylori-Induced Stomach Diseases. Helicobacter. 2015. Vol. 20. № 6. P. 460–475.
MediAl. 2019; : 55-69
Features of the human immune response to Helicobacter pylori infection
https://doi.org/10.21145/2225-0026-2019-2-55-69Abstract
Helicobacter pylori is considered the etiological agent of acute and chronic forms of gastritis, and is also capable of exerting a multifactorial effect on the host organism and on the nature of the immune response. The inflammatory response to H. pylori infection has its own characteristics. With an active course, inflammatory reactions, when the modulating effect of regulatory T-lymphocytes (T-reg) is weakened and populations of pro-inflammatory cells (T-helpers 1, 17, 22 type and follicular T-helpers) are activated, which have pronounced destructive changes in the gastric mucosa and the duodenum. guts. Macrophages, dendritic cells and neutrophils are cellular factors of the innate immune system, as well as adaptive immunity, which provides protection against infection. In turn, H. pylori uses a variety of mechanisms to evade the destruction of the host immune system. Long-term preservation of inflammation can cause local activation of mutagenesis, which initiates the development of malignant neoplasms of the gastric mucosa. A review of the host immune response to H. pylori is devoted to this analytical review.
References
1. Chen Y., Blaser M.J. Helicobacter pylori colonization is inversely associated with childhood asthma. J. Infect. Dis. 2008. Vol. 198. P. 553–560.
2. Lerner A., Arleevskaya M., Schmiedl A. et al. Microbes and viruses are bugging the gut in celiac disease. Are they friends or foes? Front. Microbiol. 2017. Vol. 8. P. 1392.
3. Khomeriki S.G. Helicobacter pylori induktor i effektor okislitel'nogo stressa v slizistoi obolochke zheludka: traditsionnye predstavleniya i novye dannye. Eksperimental'naya i klinicheskaya gastroenterologiya. 2006. № 1. C. 37–46.
4. Il'chishina T.A. Osobennosti laboratornoi diagnostiki Helicobacter pylori i klinicheskogo techeniya khronicheskogo gastrita i yazvennoi bolezni pri batsillyarno-kokkovom dismorfizme bakterii^ Avtoref. dics. ... kand. med. nauk. SPb., 2008. C. 23.
5. Isakov V.A., Domradskii I.V. Khelikobakterioz. M.: Medpraktika, 2003. S. 412.
6. Lu H., Yamaoka Y., Graham D.Y. Helicobacter pylori virulence factors: facts and fantasies. Curr. Opin. Gastroenterol. 2005. Vol. 21. P. 653–659.
7. Shiota. S., Suzuki R., Yamaoka Y. The significance of virulence factors in Helicobacter pylori. J. of digestive diseases. 2013. Vol. 14. №. 3. P. 341–349.
8. Bell G.D. Clinical practice breath tests. Br Med Bull. 1998. Vol. 54. P. 187–193.
9. Tang R.X., Luo D.J., Sun A.H., Yan J. Diversity of Helicobacter pylori isolates in expression of antigens and induction of antibodies. World J Gastroenterol. 2008. Vol. 14. № 30. P. 4816-4822.
10. Isaeva G.Sh., Valieva R.I. Biologicheskie svoistva i virulentnost' Helicobacter pylori. Minzdrav Rossii, Kazan', Rossiya. 2018. T. 20. № 1. S. 14-20.
11. Chernyavskii V.I., Biryukova S.V. i dr. Helicobacter pylori-Herpesviridae assotsiatsii v etiopatogeneze neoplasticheskikh porazhenii zheludka, sovremennye aspekty izucheniya. Anali. Mechnikovs'kogo Institutu. 2005. № 1. S. 48–62.
12. Low H.H., Gubellini F., Rivera-Calzada A. et al. Structure of a type IV secretion system. Nature. 2014. Vol. 10. R. 1038–1043.
13. Solnick J.V., Hansen L.M., Salama N.R., et al. Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc. Natl. Acad. Sci. USA. 2004. Vol. 101. P. 2106–2111.
14. Maev I.V., Samsonov A.A., Andreev D.N. Infektsiya Helicobacter pylori. M.: GEOTAR-Media, 2016. C. 256.
15. Yamaoka Y., Kita M., Kodama T., et al. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive 500 Helicobacter pylori strains. Gut 1997. Vol. 41. P. 442–45
16. Dadashzadeh K. Milani M., Somi M.H. The prevalence of Helicobacter pylori CagA and IceA genotypes and possible clinical outcomes. Acta. Medica. mediterranea. 2015. Vol. 31. P. 1345–1349.
17. Aziz F., Chen X., Yang X., Yan Q. Prevalence and correlation with clinical diseases of Helicobacter pylori cagA and vacA genotype among gastric patients from Northeast China. BioMed research international. 2014. Vol. 1. P. 201–2010.
18. Baryshnikova N.V. Aktual'nye problemy diagnostiki khelikobakterioza. Eksperimental'naya i klinicheskaya gastroenterologiya. 2009. № 2. S. 50–58.
19. Perfilova K.M., Neumoinoi N.V., Neumoinoi M.V., i dr. Geneticheskie markery N.pylori pri khelikobakter-assotsiirovannykh zabolevaniyakh. Analiticheskii obzor. Nizhnii Novgorod: FBUN NNIIEM im.akademika I.N.Blokhinoi Rospotrebnadzora, 2016. 38 s.
20. Hase K., Murakami M., Iimura M., et al. Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology. 2003. Vol. 125. № 6. P. 1613-1625.
21. Schmausser B., Andrulis M., Endrich S. et al. Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and TLR9 on the gastric epithelium in Helicobacter pylori infection. Clin. Exp. Immunol. 2004. Vol. 136. P. 521–526.
22. D’Elios M.M., Andersen L.P. Inflammation, immunity, and vaccines for Helicobacter pylori. Helicobacter. 2009. Vol. 14. P. 21–28.
23. Izcue A, Coombes JL, Powrie F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol Rev. 2006. Vol. 212. P. 256–271.
24. Kaparakis M., Philpott D.J, Ferrero R.L. Mammalian NLR proteins; discriminating foe from friend. Immunol Cell Biol. 2007. P. 495–502.
25. Chernutskaya S.P. Gervazieva V.B. Rol' immunnoi sistemy v persistentsii Helicobacter pylori. Infektsionnye bolezni. 2008. T. 6. № 2. C. 69–77.
26. Birkholz S., Schneider T., Knipp U., et al. Decreased Helicobacter pylorispecific gastric secretory IgA antibodies in infected patients. Digestion. 1998. Vol. 59. № 6. P. 638–645.
27. Gorrell R.J., Wijburg O.L., Pedersen J.S. et al. Contribution of secretory antibodies to intestinal mucosal immunity against Helicobacter pylori. Infect Immun. 2013. Vol. 81. № 10. P. 3880–3893.
28. Kononov A.V. Mestnyi immunnyi otvet na infektsiyu Helicobacter pylori. Ros. zhurn. gastroenterol., gepatol., koloproktol. 1999. T. 2. C. 15–21.
29. Liutu M., Kalimo K., Uksila J., Savolainen J. Extraction of IgE-binding components of Helicobacter pylori by immunoblotting analysis in chronic urticaria patients. Int.Arch. Allergy Immunol. 2001. Vol. 126. № 3. P. 213–217.
30. Mazurina S.A., Il'intseva N.V., Agafonov V.E., Gervazieva V.B. Antikhelikobakternye IgE antitela u detei s zabolevaniyami gastroduodenal'noi zony i soputstvuyushchei allergopatologiei. Eksperimental'naya i klinicheskaya gastroenterologiya. 2013. № 9. P. 21–25.
31. Berczi L., Sebestyen A., Fekete B., et al. IgE-containing cells in gastric mucosa with and without Helicobacter pylori infection.Pathol. Res. Pract. 2000. Vol. 196. № 12. P. 831–834.
32. Mazurina S.A., Il'intseva N.V. i dr. Immunnyi otvet slizistoi obolochki zheludka na infitsirovanie Helicobacter pylori u detei, stradayushchikh gastroduodenal'noi patologiei i allergiei. Klinicheskaya gastroenterologiya | clinical gastroenterology. 2014. T. 109. № 9. S. 30-34.
33. Dubtsova E.A. Nekotorye immunologicheskie aspekty yazvoobrazovaniya. Eksperimental'naya i klinicheskaya gastroenterologiya. 2002. T. 4. C. 9–14.
34. Chernin V.V. Yazvennaya bolezn', khronicheskii gastrit i ezofagit v aspekte disbakterioza ezofagogastroduodenal'noi zony. Eksperimental'naya i klinicheskaya gastroenterologiya. 2008. T. 3. C. 68–69.
35. Morris A.J., Ali M.R., Nicholson G.I. et al. Long-term follow up of voluntary ingestion of Helicobacter pylori. Ann. Intern. Med. 1991. Vol. 114. P. 662–663.
36. Nurgalieva Z.Z., Conner M.E., Opekun A.R. et al. B-cell and T-cell immune responses to experimental Helicobacter pylori infection in humans. Infect. Immun. 2005. Vol. 73. C. 2999–3006.
37. Warren J.R. Gastric pathology associated with Helicobacter pylori. Gastroenterol. Clin. North. Am. 2000. Vol. 29. P. 705-751.
38. Lundgren A., Stromberg E., Sjoling A. et al. Mucosal FOXP3-expressing CD4+CD25high regulatory T cells in Helicobacter pylori-infected patients. Infect. Immun. 2005. Vol. 73. C. 523–531.
39. Lee S.K., Stack A., Katzowitsch E. et al. Helicobacter pylori flagellins have very low intrinsic activity to stimulate human gastric epithelial cells via TLR5. Microbes Infect. 2003. Vol. 5. P. 1345–1356.
40. Makristathis A., Rokita E., Labigne A. et al. Highly significant role of Helicobacter pylori urease in phagocytosis and production of oxygen metabolites by human granulocytes. J Infect Dis. 1998. Vol. 177. P. 803–806.
41. Dubois A., Born T. Helicobacter pylori is invasive and it may be a facultative intracellular organism. Cell. Microbiol. 2007. Vol. 9. P. 1108–1116.
42. Fehlings M., Drobbe L., Moos V. et al. Comparative analysis of the interaction of Helicobacter pylori with human dendritic cells, macrophages, and monocytes. Infect. Immun. 2012. Vol. 80. P. 2724–2734.
43. Gobert A.P., Bambou J.C., Werts C. et al. 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. 2004. Vol. 279. P. 245–250.
44. Zheng P.Y., Jones N.L. Helicobacter pylori strains expressing the vacuolating cytotoxin interrupt phagosome maturation in macrophages by recruiting and retaining TACO (coronin 1) protein. Cell Microbiol. 2003. Vol. 5. P. 25–40.
45. Allen L.A., Allgood J.A. Atypical protein kinase C-zeta is essential for delayed phagocytosis of Helicobacter pylori. Curr. Biol. 2002. Vol. 12. P. 1762–1766.
46. Wang Y.H., Wu J.J., Lei H.Y. When Helicobacter pylori invades and replicates in the cells. Autophagy. 2009. Vol. 5. P. 540–542.
47. Rittig M.G., Shaw. B., Letley D.P. et al. Helicobacter pylori-induced homotypic phagosome fusion in human monocytes is independent of the bacterial vacA and cag status. Cell. Microbiol. 2003. Vol. 5. P. 887–899.
48. Schwartz J.T., Allen L.A. Role of urease in megasome formation and Helicobacter pylori survival in macrophages. J. Leukoc. Biol. 2006. Vol. 79. P. 1214–1225.
49. Menaker R.J., Ceponis P.J., Jones N.L. Helicobacter pylori induces apoptosis of macrophages in association with alterations in the mitochondrial pathway. Infect. Immun. 2004. Vol. 72. P. 2889–2898.
50. Basu M., Czinn S.J., Blanchard T.G. Absence of catalase reduces long-term survival of Helicobacter pylori in macrophage phagosomes. Helicobacter. 2004. Vol. 9. P. 211–216.
51. Satin B., Giuseppe del Giudice, Della Bianca V., et al. The Neutropil-activating Protein (HP-NAP) of Helicobacter pylori Is a Protective Antigen and a Major Virulence Factor. J. of Experimental Medicine. 2000. Vol. 191. P. 1467–1476.
52. Schmausser B., Josenhans C., Endrich S., et al. Downregulation of CXCR1 and CXCR2 expression on human neutrophils by Helicobacter pylori: a new pathomechanism in H. pylori infection? Infect. Immun. 2004. Vol. 72. P. 6773–6779.
53. Mahnke K., Ring S., Johnson T.S., Schallenberg S., Schonfeld K., Storn V., Bedke T., Enk A.H. Induction of immunosuppressive functions of dendritic cells in vivo by CD4+CD25+ regulatory T cells: Role of B7-H3 expression and antigen presentation. Eur. J. Immunol. 2007. Vol. 37. P. 2117–2126.
54. Necchi V., Manca R., Ricci V., Solcia E. Evidence for transepithelial dendritic cells in human H. pylori active gastritis. Helicobacter. 2009. Vol. 14. P. 208–222.
55. Mitchell P., Germain C., Fiori P.L., Khamri W., Foster G.R., Ghosh S., et al. Chronic exposure to Helicobacter pylori impairs dendritic cell function and inhibits Th1 development. Infect. Immun. 2007. Vol. 75. P. 810–819.
56. Bergman M.P., Engering A., Smits H. H., et al. Helicobacter pylori modulates the T helpercell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J. Exp. Med. 2004. Vol. 200. P. 979–990.
57. Ieni A., Barresi V., Rigoli L., et al. Morphological and Cellular Features of Innate Immune Reaction in Helicobacter pylori Gastritis: A Brief Review. Int. J. Mol. Sci. 2016. Vol. 17. P. 109.
58. Bagheri N., Azadegan-Dehkordi F., Rahimian G., Rafieian-Kopaei M., Shirzad H. Role of regulatory T-cells in different clinical expressions of Helicobacter pylori infection. Arch Med Res. 2016. Vol. 47. P. 245–254.
59. Razavi A., Bagheri N., Azadegan-Dehkordi F., Shirzad M., Rahimian G., Rafieian-Kopaei M., et al. Comparative Immune Response in Children and Adults with H. pylori Infection. J. Immunol. Res. 2015. Vol. 2015. P. 315957.
60. Bagheri N., Salimzadeh L., Shirzad H. The role of T helper 1-cell response in Helicobacter pylori-infection. Microbial Pathogenesis. 2018. Vol. 123. P. 1–8.
61. Del Giudice G., Covacci A., Telford J.L., Montecucco C., Rappuoli R. The design of vaccines against Helicobacter pylori and their development. Annu. Rev. Immunol. 2001. Vol.19. P. 523–563.
62. Bimczok D., Clements R.H., Waites K.B., Novak L., Eckhoff D.E., Mannon P.J., et al. Human primary gastric dendritic cells induce a Th1 response to H. pylori. Mucosal Immunol. 2010. Vol. 3. P. 260–269.
63. Tourani M., Habibzadeh M., Karkhah A., Shokri-Shirvani J., Barari L., Nouri H.R. Association of TNFalpha but not IL-1beta levels with the presence of Helicobacter pylori infection increased the risk of peptic ulcer development. Cytokine. 2018. Vol. 110. P. 232–236
64. Freire de Melo F., Rocha G.A., Rocha A.M., Teixeira K.N., Pedroso S.H., Pereira Junior J.B., et al. Th1 immune response to H. pylori infection varies according to the age of the patients and influences the gastric inflammatory patterns. Int. J. Med. Microbiol. 2014. Vol. 304. P. 300–306.
65. Annunziato F., Romagnani S. The transient nature of the Th17 phenotype. Eur. J. Immunol. 2010. Vol. 40. P. 3312–3316.
66. Acosta-Rodriguez E.V., Rivino L., Geginat J. et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T-helper memory cells. Nat. Immunol. 2007. Vol. 8. P. 639–646.
67. Adamsson J., Ottsjo L.S., Lundin S.B., Svennerholm A.M., Raghavan S. Gastric expression of IL-17A and IFNgamma in Helicobacter pylori infected individuals is related to symptoms. Cytokine. 2017. Vol. 99. P. 30–34.
68. Yokota K., Kobayashi K., Kawahara Y., Hayashi S., Hirai Y., Mizuno M., et al. Gastric ulcers in SCID mice induced by Helicobacter pylori infection after transplanting lymphocytes from patients with gastric lymphoma. Gastroenterology. 1999. Vol. 117. P. 893–899.
69. 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. Vol. 110. P. 165–175.
70. Matveichev A.V., Talaev V.Yu., Evplova I.A. fiziologiya i funktsionirovanie T-khelperov 17-go tipa. Uspekhi sovremennoi biologii. 2016. T. 136. № 3. S. 285–300.
71. Caruso F. Pallone, Monteleone G. Emerging role of IL-23/IL-17 axis in Helicobacter pylori-associated pathology. J Gastroenterol. 2007. Vol. 14. P. 5547–5551. 7
72. Luzza F., Parrello T., Monteleone G. et al. Up-Regulation of IL-17 Is Associated with Bioactive IL-8 Expression in Helicobacter pylori-Infected Human Gastric Mucosa. J. of Immun. 2019. Vol. 165. P. 5332–5337.
73. Pappu R., Rutz S., Ouyang W. Regulation of epithelial immunity by IL-17 family cytokines. Trends Immunol. 2012. Vol. 33. P. 343–349.
74. Ayraud S., Janvier B., Fauchere J.L. Experimental colonization of mice by fresh clinical isolates of Helicobacter pylori is not influenced by the cagA status and the vacA genotype. FEMS Immunol. Med Microbiol. 2002. Vol. 34. P. 169–172.
75. Jadidi-Niaragh F., Mirshafiey A. Th17 sell, the new player of neuroinflammatory process in multiple sclerosis. Scand. J. Immunol. 2011. Vol. 74. P. 1–13.
76. Martin B., Hirota K., Cua D.J. et al. Interleukin-17-producing T cells selectively expand in response to pathogen products and environmental signals. Immunity. 2009. Vol. 31. P. 321–330.
77. Tanaka S., Nagashima H., Cruz M. et al. Interleukin-17C in human Helicobacter pylori gastritis. Infect Immun. 2017. Vol. 85. P. 389-417.
78. Yamaoka Y., Kita M., Kodama T. et al. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive 500 Helicobacter pylori strains. Gut 1997. Vol. 41. P. 442–45
79. Gu C., Wu L., Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013. Vol. 64. P. 477–485.
80. Song X, Gao H, Lin Y. et al. Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. Immunity. 2014. Vol. 40. P. 140–152.
81. Uhlen M., Oksvold P., Fagerberg L. et al. Towards a knowledge-based Human Protein Atlas. Nat Biotech 2010. Vol. 28. P. 1248–1250.
82. Shi Y., Liu X.F., Zhuang Y., Zhang J.Y., Liu T., Yin Z. et al. Helicobacter pylori induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice. J. Immunol. 2010. Vol. 184. P. 5121–5129.
83. Tsyganova M.I., Talaeva M.V., Talaev V.Yu. i dr. Vliyanie Helicobacter pylori na soderzhanie provospalitel'nykh T-kletochnykh tsitokinov i produtsiruyushchikh ikh subpopulyatsii. Analiz riska zdorov'yu. 2018. № 3. S. 120–127.
84. Konorev M.R. Immunnyi otvet pri persistentsii N.Pylori na slizistykh obolochkakh s zheludochnym epiteliem. Immunopatologiya, allergologiya, infektologiya. 2010. № 2. C. 55–62.
85. Leber A., Abedi V., Hontecillas R. et al. Bistability analyses of CD4+ T follicular helper and regulatory cells during Helicobacter pylori infection. J Theor Biol. 2016. Vol. 398. P. 74–84.
86. Talaeva M.V., Talaev V.Yu. Voronina E.V. i dr. Ekspressiya khemokinovykh retseptorov na T-khelperakh krovi pri zabolevaniyakh, assotsiirovannykh s H. pylori. Kh Vserossiiskaya nauchno-prakticheskaya konferentsiya molodykh uchenykh i spetsialistov Rospotrebnadzora «Sovremennye problemy epidemiologii, mikrobiologii i gigieny». 2018. S. 275–279.
87. Zavros Y., Rathinavelu S., Kao J.Y. et al. Treatment of Helicobacter gastritis with IL-4 requires somatostatin. Proc. Natl. Acad. Sci. USA. 2003. Vol. 100. P. 12944–12949.
88. Ceponis P.J., McKay D.M., Menaker R.J. et al. Helicobacter pylori infection interferes with epithelial Stat6-mediated interleukin-4 signal transduction independent of cagA, cagE, or VacA. J. Immunol. 2003. Vol. 171. P. 2035–2041.
89. Watanabe K., Murakami K., Sato R. et al. CTLA-4 blockade inhibits induction of Helicobacter pylori-associated gastritis in mice. Clin. Exp. Immunol. 2004. Vol. 135. P. 29–34.
90. Ismail H.F., Zhang J., Lynch R.G. et al. Role for complement in development of Helicobacter-induced gastritis in interleukin-10-deficient mice. Infect. Immun. 2003. Vol. 71. P. 7140–7148.
91. Rad R., Brenner L., Bauer S., Schwendy S., Layland L., da Costa C.P. et al. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology. 2006. Vol. 131. P. 525–537.
92. Jang T.J. The number of Foxp3-positive regulatory T cells is increased in Helicobacter pylori gastritis and gastric cancer. Pathol Res Pract. 2010. Vol. 206. P. 34–38.
93. Sun X., Zhang M., El-Zaatari M., Huffnagle G.B., Kao J.Y. CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis. Helicobacter. 2016. P. 1–9.
94. Guiney D.G., Hasegawa P., Cole S.P. Helicobacter pylori preferentially induces interleukin 12 (IL-12) rather than IL-6 or IL-10 in human dendritic cells. Infect. Immun. 2003. Vol. 710. P. 4163–4166.
95. Hoffman P.S., Vats N., Hutchison D. et al. Development of an interleukin-12 deficient mouse model that is permissive for colonization by a motile KE26695 strain of Helicobacter pylori. Infect. Immun. 2003. Vol. 71. P. 2534–2541.
96. Holck S., Norgaard A., Bennedsen M. et al. Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacteria load. FEMS Immunol. Med. Microbiol. 2003. Vol. 36. P. 175–180.
97. Matveichev A.V., Talaeva M.V., Talaev V.Yu. Vliyanie Helicobacter pylori na differentsirovku T-regulyatornykh kletok. Analiz riska zdorov'yu. 2017. № 1. S. 21–28.
98. Jafarzadeh A., Larussa T., Nemati M., Jalapour S. T cell subsets play an important role in the determination of the clinical outcome of Helicobacter pylori infection. Microb Pathog. 2018. Vol. 116. P. 227–236.
99. Bagheri N., Azadegan-Dehkordi F., Shirzad H/ et al. (2015) The biological functions of IL-17 in different clinical expressions of Helicobacter pyloriinfection. Microb. Pathog. 2015. Vol. 81. P. 33–38.
100. Wan Y. Multi-tasking of helper T cells.Immunology 2010. Vol. 130. P. 166–171.
101. Zhuang Y. A pro-inflammatory role for Th22 cells in Helicobacter pyloriassociated gastritis. Gut. 2014. P. 1368–1378.
102. Shamsdin S.A., Alborzi A., Rasouli M. et al. Alterations in Th17 and the respective cytokine levels in Helicobacter pylori-Induced Stomach Diseases. Helicobacter. 2015. Vol. 20. № 6. P. 460–475.
