REGULATION OF IMMUNE RESPONSE AGAINST MYCOBACTERIUM TUBERCULOSIS BY THE POPULATION OF REGULATORY DENDRITIC CELLS

Cover Page


Cite item

Full Text

Abstract

On the background of a high level of genetic susceptibility to tuberculosis infection (TB), granulomatous reactions in the lung  tissue fail to effectively isolate infection foci and rather result in  diffuse pathology, confluence of granulomata and  formation of  necrotic zones. Uncontrolled inflammation severely affect breathing  function of the lung. Thus, effective disease control requires a good  balance between protective and pathogenic immune responses.  Immature regulatory dendritic cells (DCreg) and regulatory T  lymphocytes (Treg) represent a pool of important cellular regulators  of inflammation. Earlier we have demonstrated that stromal lung  cells support development of CD11b+CD11clowCD103– DCreg from  their bone marrowderived precursors in in vitro cultures. In addition,  significantly larger population size and more rapid  development of the lung CD4+Foxp3+ Treg cells characterize TB- resistant B6 mice compare to their TB-susceptible I/St counterparts.  Here, we report that adoptive transfer of DCreg cells into TB-infected I/St mice is capable to enlarge the population of Treg cells in the  lungs. This, in turn, attenuates lung pathology, decreases  mycobacterial multiplication and diminishes lung infiltration with  neutrophils, i.e., selectively restricts the population of cell largely  responsible for TB pathogenesis. The key difference in lung  pathology between DCreg recipients and control animals was the  lack of tissue-destructive foci and necrotic zones in the former  group. Meanwhile, the groups of mice did not differ in production of  regulatory (IL-10 and TGF-β) and key inflammatory (IFNγ and IL-6)  cytokines by lung cells. The latter result suggests that contact rather  than secretory mechanisms underlie moderate attenuation of  the TB process in the lungs of mice with an elevated lung Treg level,  given that plethora of such mechanisms were described for Treg  functioning. Although therapeutic effects were relatively weak, our  results indicate that cell therapy approaches are applicable to  regulation of lung tissue inflammation during TB course. 

About the authors

E. I. Rubakova

Central Research Institute of Tuberculosis

Email: fake@neicon.ru

PhD (Biology), Senior Researcher, Laboratory of Immunogenetics, Central Research Institute of Tuberculosis, Moscow, Russian Federation

Russian Federation

M. A. Kapina

Central Research Institute of Tuberculosis

Email: fake@neicon.ru

PhD (Biology), Senior Researcher, Laboratory of  Immunogenetics, Central Research Institute of Tuberculosis, Moscow, Russian Federation

Russian Federation

N. N. Logunova

Central Research Institute of Tuberculosis

Email: fake@neicon.ru

PhD (Medicine), Senior Researcher, Laboratory of  Immunogenetics, Central Research Institute of Tuberculosis, Moscow, Russian Federation

Russian Federation

K. B. Majorov

Central Research Institute of Tuberculosis

Email: fake@neicon.ru

PhD (Biology), Senior Researcher, Laboratory of  Immunogenetics, Central Research Institute of Tuberculosis, Moscow, Russian Federation

Russian Federation

A. S. Apt

Central Research Institute of Tuberculosis

Author for correspondence.
Email: alexapt0151@gmail.com

PhD, MD (Biology), Professor, Head of the Laboratory of  Immunogenetics, Central Research Institute of Tuberculosis, Moscow, Russian Federation

107564, Russian Federation, Moscow, Yauzskaya alley, 2

Phone: +7 (812) 785-90-72 (office)

Russian Federation

References

  1. Allie N., Grivennikov S.I., Keeton R., Hsu N.J., Bourigault M.L., Court N., Fremond C., Yeremeev V., Shebzukhov Y., Ryffel B., Nedospasov S.A., Quesniaux V.F.J., Jacobs M. Prominent role for T cell-derived tumour necrosis factor for sustained control of Mycobacterium tuberculosis infection. Sci. Rep., 2013, vol. 3, no. 1809, 14 p. doi: 10.1038/srep01809
  2. Cooper A.M. T cells in mycobacterial infection and disease. Curr. Opin. Immunol., 2009, vol. 21, iss. 4, pp. 378–384. doi: 10.1016/j.coi.2009.06.004
  3. Dorhoi A., Reece S.T., Kaufmann S.H.E. For better or for worse: the immune response against Mycobacterium tuberculosis balances pathology and protection. Immunol. Rev., 2011, vol. 240, iss. 1, pp. 235–251. doi: 10.1111/j.1600-065X.2010.00994.x
  4. Eruslanov E.B., Lyadova I.V., Kondratieva T.K., Majorov K.B., Scheglov I.V., Orlova M.O., Apt A.S. Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice. Infect. Immun., 2005, vol. 73, no. 3, pp. 1744–1753. doi: 10.1128/IAI.73.3.1744-1753.2005
  5. Eruslanov E.B., Majorov K.B., Orlova M.O., Mischenko V.V., Kondratieva T.K., Apt A.S., Lyadova I.V. Lung cell responses to M. tuberculosis in genetically susceptible and resistant mice following intratracheal challenge. Clin. Exp. Immunol., 2004, vol. 135, no. 1, pp. 19–28.
  6. Flynn J.L., Chan J., Triebold K.J., Dalton D.K., Stewart T.A., Bloom B.R. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J. Exp. Med., 1993, vol. 176, no. 6, pp. 2249–2254.
  7. Kapina M.A., Rubakova E.I., Majorov K.B., Logunova N.N., Apt A.S. Capacity of lung stroma to educate dendritic cells inhibiting mycobacteria-specific T-cell response depends upon genetic susceptibility to tuberculosis. PLoS One, 2013, vol. 8, no. 8: e72773. doi: 10.1371/journal.pone.0072773
  8. Kondratieva E.V., Logunova N.N., Majorov K.B., Averbakh M.M., Apt A.S. Host genetics in granuloma formation: human-like lung pathology in mice with reciprocal genetic susceptibility to M. tuberculosis and M. avium. PLoS ONE, 2010, vol. 6, no. 5: e10515. doi: 10.1371/journal.pone.0010515
  9. Leepiyasakulchai C., Ignatowicz L., Pawlowski A., Källenius G., Sköld M. Failure to recruit anti-inflammatory CD103+ dendritic cells and a diminished CD4+ Foxp3+ regulatory T cell pool in mice that display excessive lung inflammation and increased susceptibility to Mycobacterium tuberculosis. Infect. Immun., 2012, vol. 80, no. 3, pp. 1128–1139. doi: 10.1128/IAI.05552-11
  10. Liang B., Workman C., Lee J., Chew C., Dale B.M., Colonna L., Flores M., Li N., Schweighoffer E., Greenberg S., Tybulewicz V., Vignali D., Clynes R.. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J. Immunol., 2008, vol. 180, no. 9, pp. 5916–5926. doi: 10.4049/jimmunol.180.9.5916
  11. Logunova N.N., Korotetskaya M.V., Polshakov V.I., Apt A.S. The QTL within the H2 complex involved in the control of tuberculosis infection in mice is the classical class II H2- Ab1 gene. PLoS Genet., 2015, vol. 11, no. 11: e1005672. doi: 10.1371/journal.pgen.1005672
  12. Lutz M.B., Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol., 2002, vol. 23, no. 9, pp. 445–449.
  13. Maldonado R.A., von Andrian U.H. How tolerogenic dendritic cells induce regulatory T cells. Adv. Immunol., 2010, vol. 108, pp. 111–165. doi: 10.1016/B978-0-12-380995-7.00004-5
  14. O’Garra A., Redford P.S., McNab F.W., Bloom C.I., Wilkinson R.J., Berry M.P. The immune response in tuberculosis. Ann. Rev. Immunol., 2013, vol. 31, pp. 475–527. doi: 10.1146/annurev-immunol-032712-095939
  15. Owens B.M., Kaye P.M. Stromal cell induction of regulatory dendritic cells. Front. Immunol., 2012, vol. 3, 6 p. doi: 10.3389/fimmu.2012.00262
  16. Qureshi O.S., Zheng Y., Nakamura K., Attridge K., Manzotti C., Schmidt E.M., Baker J., Jeffery L.E., Kaur S., Briggs Z., Hou T.Z., Futter C.E., Anderson G., Walker L.S.K., Sansom D.M. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science, 2011, vol. 332, iss. 6029, pp. 600–603. doi: 10.1126/science.1202947
  17. Radaeva T.V., Kondratieva E.V., Sosunov V.V., Majorov K.B., Apt A.S. A human-like TB in genetically susceptible mice followed by the true dormancy in a Cornell-like model. Tuberculosis (Edinb.), 2008, vol. 88, iss. 6, pp. 576–585. doi: 10.1016/j.tube.2008.05.003
  18. Reece S.T., Kaufmann S.H.E. Floating between the poles of pathology and protection: can we pin down the granuloma in tuberculosis? Curr. Opin. Microbiol., 2012, vol. 15, iss. 1, pp. 63–70. doi: 10.1016/j.mib.2011.10.006
  19. Rook G.A.W., Hernandez-Pando R. The pathogenesis of tuberculosis. Ann. Rev. Microbiol., 1996, vol. 50, pp. 259–284. doi: 10.1146/annurev.micro.50.1.259
  20. Sakaguchi S., Wing K., Onishi Y., Prieto-Martin P., Yamaguchi T. Regulatory T cells: how do they suppress immune responses? Int. Immunol., 2009, vol. 21, no. 10, pp. 1105–1111. doi: 10.1093/intimm/dxp095
  21. Sakai S., Kauffman K.D., Sallin M.A., Sharpe A.H., Young H.A., Ganusov V.V., Barber D.L. CD4 T cell-derived IFNγ plays a minimal role in control of pulmonary Mycobacterium tuberculosis infection and must be actively repressed by PD-1 to prevent lethal disease. PLoS Pathog., 2016, vol. 12, no. 5: e1005667. doi: 10.1371/journal.ppat.1005667
  22. Shepelkova G., Evstifeev V., Majorov K., Bocharova I., Apt A. Therapeutic effect of recombinant mutated interleukin 11 in the mouse model of tuberculosis. J. Infect. Dis., 2016, vol. 214, iss. 3, pp. 496–501. doi: 10.1093/infdis/jiw176
  23. Smits H.H., de Jong E.C., Wierenga E.A., Kapsenberg M.L. Different faces of regulatory DCs in homeostasis and immunity. Trends Immunol., 2005, vol. 26, no. 3, pp. 123–129. doi: 10.1016/j.it.2005.01.002
  24. Steinman R.M., Hawiger D., Nussenzweig M.C. Tolerogenic dendritic cells. Annu. Rev. Immunol., 2003, vol. 21, pp. 685–711. doi: 10.1146/annurev.immunol.21.120601.141040
  25. Torrado E., Robinson R.T., Cooper A.M. Cellular response to mycobacteria: balancing protection and pathology. Trends Immunol., 2011, vol. 32, no. 2, pp. 66–72. doi: 10.1016/j.it.2010.12.001
  26. Tsai M.C., Chakravarty S., Zhu G., Xu J., Tanaka K., Tufariello J., Flynn J., Chan J. Characterization of the tuberculous granuloma in murine and human lungs: cellular composition and relative tissue oxygen tension. Cell. Microbiol., 2006, vol. 8, no. 2, pp. 218– 232. doi: 10.1111/j.1462-5822.2005.00612.x
  27. Wang J., Lu Z.H., Gabius H.J., Rohowsky-Kochan C., Ledeen R.W., Wu G. Cross-linking of GM1 ganglioside by galectin-1 mediates regulatory T cell activity involving TRPC5 channel activation: possible role in suppressing experimental autoimmune encephalomyelitis. J. Immunol., 2009, vol. 182, no. 7, pp. 4036–4045. doi: 10.4049/jimmunol.0802981
  28. Yeremeev V.V., Linge I.A., Kondratieva T.K., Apt A.S. Neutrophils exacerbate tuberculosis infection in genetically susceptible mice. Tuberculosis (Edinb.), 2015, vol. 95, no. 4, pp. 447– 451. doi: 10.1016/j.tube.2015.03.007.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2018 Rubakova E.I., Kapina M.A., Logunova N.N., Majorov K.B., Apt A.S.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

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

About Cookies