Influence exerted by helicobacter pylori on regulatory t-cells differentiation
А.V. Matveichev1, М.V. Talaeva1, V.Yu. Talaev1, N.V. Neumoina1, K.M. Perfilova1, D.G. Lapaev2, E.V. Mokhonova1, M.I. Tsyganova1, V.N. Koptelova1, Z.I. Nikitina1, V.A. Lapin1,3, D.A. Melent'ev3
1 Nizhniy Novgorod Research Institute of Epidemiology and Microbiology named after Academician I.N. Blokhina, 71m Malaya Yamskaya Str., Nizhniy Novgorod, 603950, Russian Federation
2 City clinical hospital No.7, 76/1, Peterburgskoye highway, Tver, 170036, Russian Federation
3 Nizhniy Novgorod National Research State University named after N.I. Lobachevskiy, 23, Gagarina avenue, Nizhniy Novgorod, 603022, Russian Federation
Estimating risks of infections induced by gram-negative Helicobacter pylori, is a vital problem for healthcare due to wide spread of the agent and wide range of induced pathologies which include malignant neoplasms in gastrointestinal tract.
The agent is prone to long-term chronic persistence despite its "fragility" and its being greatly demanding to culturing conditions. The persistence issue is of special interest here as it is related to data on Helicobacter pylori capability to change immune response in infected people inducing suppressive regulatory immune reactions which are more favorable for the agent, both in stomach and in a whole body. Our research goal was to estimate Helicobacter pylori capability to induce differentiation of regulatory CD4+CD25+FoxP3+ human T-cells as basic mediators of immune response regulation under direct contact between bacteria and T-cells without any participation of most professional antigen-presenting cells. Our research objects were clinical isolates of Helicobacter pylori and T-lymphocytes samples taken from people who didn't have Helicobacter pylori-infection in their case history; isolates and samples were jointly cultivated in vitro. We applied cytofluorometry to estimate changes in regulatory T-cells content. We detected that if T-lymphocytes and Helicobacter pylori were jointly cultivated during 18 hours in ratios from 1:10 to 1:50, regulatory T-cells content in cultures increased 2.12 times on average. This effects doesn't require any dendritic cells in a culture and obviously affects T-lymphocytes which are originally committed to regulatory T-cells in their development. Also, in our opinion, influence exerted on regulatory T-cells differentiation is a specific feature of Helicobacter pylori.
- Zhebrun A.B., Svarval' A.V., Ferman R.S., Goncharova L.B. Metody laboratornoi diagnostiki infektsii, obuslovlennoi Helicobacter pylori: posobie dlya vrachei [Laboratory diagnostics techniques for infection induced by Helicobacter pylori: Aid for physicians]. St. Petersburg, FBUN NIIEM imeni Pastera Publ., 2014, 60 p. (in Rus-sian).
- 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.
- Arnold I.C., Dehzad N., Reuter S., Martin H. [et al.]. 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.
- Fehri L.F., Koch M., Belogolova E., Khalil H. [et al.]. Helicobacter pylori induces miR-155 in T Cells in a cAMP-Foxp3-dependent manner. PLoS One, 2010, vol. 5, no. 3, e9500.
- Käbisch R., Mejías-Luque R., Gerhard M., Prinz C. Involvement of Toll-like receptors on Helicobacter pylori-induced immunity. PLoS One, 2014, vol. 9, no. 8, e104804.
- Lundgren A., Stromberg E., Sjoling A., Lindholm C. [et al.]. Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infect. Immun, 2005, vol. 73, no. 1, pp. 523–531.
- Necchi V., Manca R., Ricci V., Solcia E. Evidence for transepithelial dendritic cells in human H. pylori active gastritis. Helicobacter, 2009, vol. 14, no. 3, pp. 208–222.
- 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.
- Raghavan S., Quiding-Järbrink M. Immune modulation by regulatory T cells in Helicobacter pylori-associated diseases. Endocr. Metab. Immune. Disord. Drug. Targets, 2012, vol. 12, no. 1, pp. 71–85.
- Romi B., Soldaini E., Pancotto L., Castellino F., Del Giudice G., Schiavetti F. Helicobacter pylori induces activation of human peripheral γδ+ T lymphocytes. PLoS One, 2011, vol. 6, no. 4, e19324.
- Rosenplänter C., Sommer F., Kleemann P., Belkovets A. [et al.]. Helicobacter pylori polyclonally activates murine CD4 (+) T cells in the absence of antigen-presenting cells. Eur. J. Immunol, 2007, vol. 37, no. 7, pp. 1905–1915.
- Sakaguchi S., Wing K., Yamaguchi T. Dynamics of peripheral tolerance and immune regulation mediated by Treg. Eur. J. Immunol, 2009, vol. 39, no. 9, pp. 2331–2336.
- Sanchez A.M., Yang Y. The role of natural regulatory T cells in infection. Immunol. Res, 2011, vol. 49, no. 1-3, pp. 124–134.
- Shiu J., Blanchard T.G. Dendritic cell function in the host response to Helicobacter pylori infection of the gastric mucosa. Pathog. Dis, 2013, vol. 67, no. 1, pp. 46–53.
- Whiteside T.L. The role of regulatory T cells in cancer immunology. Immunotargets. Ther, 2015, vol. 4, pp. 159–171.
- Windle H.J., Ang Y.S., Athie-Morales V., McManus R. [et al.]. 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.