Influence exerted by helicobacter pylori on concentrations of anti-inflammatory т-cell cytokines and sunpopulations that produce them

View or download the full article: 
UDC: 
616.98: 579.835.12
Authors: 

M.I. Tsyganova1, M.V. Talaeva1, V.Yu. Talaev1, N.V. Neumoina1, K.M. Perfilova1, E.V. Mokhonova 1,V.A. Lapin1,2, D.A. Melent'ev1,2

Organization: 

1Nizhniy Novgorod Research Institute of Epidemiology and Microbiology named after Academician I.N. Blokhina, 71 Malaya Yamskaya Str., Nizhniy Novgorod, 603950, Russian Federation
2Nizhniy Novgorod National Research State University named after N.I. Lobachevskiy, 23, Gagarina avenue, Nizhniy Novgorod, 603022, Russian Federation

Abstract: 

Helicobacter pylori is a widely spread pathogenic microorganism. It penetrates the mucous tunic of the stomach and the duodenum and causes diseases in the gastrointestinal tract, including oncologic ones. This agent is able to be chronically persistent in a body and frequently there are no apparent symptoms of it; therefore, it is difficult to detect this pathogen in due time. Risk analysis related to occurrence and development of various pathologies associated with Helicobacter pylori, revealed that their clinical course was to a great extent determined by an immune response that emerged after infection. There are data that Helicobacter pylori is able to influence protective immune reactions making their balance to move to an increase in immune-suppressive components, for example, increased concentrations of T-regulatory cells and cytokines produced by them. However, some data can be found on Helicobacter pylori ability to induce anti-inflammatory responses which include those associated with T-helpers of the 1st and 17th types. Our research goal was to reveal peculiarities of effects produced by this pathogen on γ-interferon as one of basic products by 1st type T-helpers and on contents of the 17th type T-helpers determined as cells belonging to CD4+CD161+ and CD4+IL17+ phenotypes under direct contacts between bacteria and lymphocytes. Our research objects were clinical isolates of Helicobacter pylori and blood samples taken from people without helicobacter infection in their case history. We extracted lymphocytes with immunomagnetic separation out of mononuclear blood cells obtained via functioning in density gradient. Their concentrations were assessed with cytofluorometry; cytokines products, with enzyme-linked immunosorbent assay. We showed that CD4+CD161+ and CD4+IL17+ cells content didn't change when they were cultivated together for 18 hours under influence exerted by Helicobacter pylori, while products of γ-interferon increased considerably. It can probably be related to activation of the 1st type T-helpers under effects produced by direct contact with bacteria. However, we didn't detect any activation of the 17th type T-helpers. Therefore, we can assume that effects produced by Helicobacter pylori on T-helpers under direct contact cause a response in a form of the 1st type T-helpers activation.

Keywords: 
Helicobacter pylori, lymphocytes, Т-helpers, differentiation, co-stimulation, антитела, flow cytofluorometry, cell cultures
TsyganovaM.I., Talaeva M.V., Talaev V.Yu., Neumoina N.V., Perfilova K.M., Mokhonova E.V., Lapin V.A., Melent'ev D.A. Influence exerted by helicobacter pylori on concentrations of anti-inflammatory т-cell cytokines and sunpopulations that produce them. Health Risk Analysis, 2018, no. 3, pp. 120–127. DOI: 10.21668/health.risk/2018.3.13.eng
References: 
  1. Van der Sloot K.W.J., Amini M., Peters V., Dijkstra G., Alizadeh B.Z. Inflammatory bowel diseases: review of known environmental protective and risk factors involved. Inflamm Bowel Dis., 2017, vol. 9, pp. 1499–1509.
  2. Pachathundikandi S.K., Müller A., Backert S. Inflammasome activation by Helicobacter pylori and its Implications for persistence and immunity. Curr. Top. Microbiol. Immunol., 2016, vol. 397, pp. 117–131.
  3. Rosenplänter C., Sommer F., Kleemann P., Belkovets A., Schmidt A., Lohoff M. Helicobacter pylori polyclonally ac-tivates murine CD4+ T-cells in the absence of antigen-presenting cells. Eur. J. Immunol., 2007, vol. 37, no. 7, pp. 1905–1915.
  4. Lerner A., Arleevskaya M., Schmiedl A., Matthias T. Microbes and viruses are bugging the gut in celiac disease. Are they friends or foes? Front Microbiol., 2017, vol. 8, pp. 1392.
  5. Chen Y., Blaser M.J. Helicobacter pylori colonization is inversely associated with childhood asthma. J. Infect. Dis., 2008, vol. 198, pp. 553–560.
  6. Bartels L.E., Jepsen P., Christensen L.A., Gerdes L.U., Vilstrup H., Dahlerup J.F. Diagnosis of Helicobacter Pylori in-fection is associated with lower prevalence and subsequent incidence of Crohn’s disease. Journal of Crohn's and Colitis, 2016, vol. 10, no. 4, pp. 443–448.
  7. Arnold I.C., Dehzad N., Reuter S., Martin H., Becher B., Taube C., Müller A. Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. Journal Clin. Invest., 2011, vol. 121, no. 8, pp. 3088–3093.
  8. Amedei A., Codolo G., Del Prete G., de Bernard M., D'Elios M.M. The effect of Helicobacter pylori on asthma and allergy. Journal Asthma. Allergy, 2010, vol. 3, pp. 139–147.
  9. Bamford K.B., Fan X., Crowe Sh.E., Leary J.F., Gourley W.K., Luthra G.K., Brooks E.G., Graham D.Y., Reyes V.E., Ernst P.B. Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T-helper cell 1 phenotype. Gastroenter-ology,1998, vol. 114, no. 3, pp. 482–492.
  10. Tarkkanen J., Kosunen T.U, Saksela E. Contact of lymphocytes with Helicobacter pylori augments natural killer cell activity and Induces Production of Gamma Interferon. Infection and immunity, 1993, vol. 61, no. 7, pp. 3012–3016.
  11. Tsai H.-F., Hsu P.-N. Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric in-flammation and mucosal pathology. Cellular & Molecular Immunology, 2010, vol. 7, pp. 255–259.
  12. Matveichev А.V., Talaeva М.V., Talaev V.Yu., Neumoina N.V., Perfilova K.M., Lapaev D.G., Mokhonova E.V., Tsyganova M.I., Koptelova V.N., Nikitina Z.I., Lapin V.A., Melent'ev D.A. Influence exerted by Helicobacter pylori on regulatory t-cells differentiation. Health Risk Analysis, 2017, no. 1, pp. 21–28. DOI: 10.21668/health.risk/2017.1.03.eng
  13. Windle H.J., Ang Y.S., Athie-Morales V., McManus R., Kelleher D. Human peripheral and gastric lymphocyte responses to Helicobacter pylori NapA and AphC differ in infected and uninfected individuals. Gut., 2005, vol. 54, no. 1, pp. 25–32.
  14. Käbisch R., MejíasLuque R., Gerhard M., Prinz C. Involvement of Toll-like receptors on Helicobacter pylori-induced immunity. PLoS One, 2014, vol. 9, no. 8, pp. e104804.
  15. Shiu J., Blanchard T.G. Dendritic cell function in the host response to Helicobacter pylori infection of the gastric mu-cosa. Pathog. Dis., 2013, vol. 67, no. 1, pp. 46–53.
  16. Tanaka S., Nagashima H., Cruz M., Uchida T., Uotani T., Jiménez Abreu J.A., Mahachai V., Vilaichone R., Ratanachu-ek T., Tshering L., Graham D.Y., Yamaoka Y. Interleukin-17C in human Helicobacter pylori gastritis. Infect Immun., 2017, vol. 85, no. 10, pp. e00389–e00417.
  17. Permin H., Andersen L.P. Inflammation, immunity, and vaccines for Helicobacter infection. Helicobacter, 2005, vol. 10, no. 1, pp. 21–25.
  18. Huter E.N., Stummvoll G.H., DiPaolo R.J., Glass. D.D., Shevach E.M. Pre-differentiated Th1 and Th17 effector T cells in autoimmune gastritis: ag-specific regulatory T cells are more potent suppressors than polyclonal regulatory T cells. Int. Im-munopharmacol., 2009, vol. 9, no 5, pp. 540–545.
  19. Pravada N.S., Budritskii A.M. Kompleksnaya terapiya s primeneniem immunotropnykh preparatov pri tuberkuleze i sistema interferona-gamma [Complex therapy with the use of immune preparations in tuberculosis and interferon-gamma system]. Vestnik Vitebskogo gosu-darstvennogo meditsinskogo universiteta, 2015, vol. 14, no. 4, pp. 5–14 (in Russian).
  20. Bazzazi H., Aghaei M., Memarian A., Asgarian-Omran H., Behnampour N., Yasdani Y. Th1-Th17 ratio as a new in-sight in rheumatoid arthritis disease. Iran J. Allergy Asthma Immunol., 2018, vol. 17, no. 1, pp. 68–77.
  21. Bar-dakhch'yan E.A., Lomov S.Yu., Kharlanova N.G., Kamneva N.V. Rol' Helicobacter Pylori pri razvitii ekstragastro-duodenal'nykh zabolevanii [Role of helicobacter pylori in different gastroduodenal diseases]. Eksperimental'naya i klinicheskaya gastroenterologiya, 2005, no. 3, pp. 20–27 (in Russian).
  22. Lutskii A.A., Zhirkov A.A., Lobzin D.Yu., Rao M., Alekseeva L.A., Meirer M., Lobzin Yu.V. Interferon-γ: biologicheskaya funktsiya i znachenie dlya diagnostiki kletochnogo immunno-go otveta [Interferon-y: biological function and ap-plicationfor study of cellular immune response]. Zhurnal infektologii, 2015, vol. 7, no. 4, pp. 10–22 (in Russian).
  23. Miao J., Zhang K., Qiu F., Li T., Lv M., Guo N., Han Q., Zhu P. Percentages of CD4+CD161+ and CD4−CD8−CD161+ T сells in the synovial fluid are correlated with disease activity in rheumatoid arthritis. Mediators Inflamm, 2015, vol. 2015, P ID 563713.
  24. Church L.D., Filer A.D., E Hidalgo., Howlett K.A., Thomas A.M.C., Rapecki S., Scheel-Toellner D., Buckley C.D., Raza K. Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression. Arthritis Res. Ther., 2010, vol. 12, no. 5, pp. R184.
  25. Shen H., Goodall J.C, Hill Gaston H.J.S. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis & Rheumatism., 2009, vol. 60, no. 6, pp. 1647–1656.
Received: 
20.06.2018
Accepted: 
20.09.2018
Published: 
30.09.2018

You are here