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

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 inflam...

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Autores principales:	E. I. Rubakova, M. A. Kapina, N. N. Logunova, K. B. Majorov, A. S. Apt
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2018
Materias:	dcreg treg tuberculosis experimental model lung pathology Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/4465056cbbb64025949644f0f30876ee
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spelling	oai:doaj.org-article:4465056cbbb64025949644f0f30876ee2021-11-22T07:09:49ZREGULATION OF IMMUNE RESPONSE AGAINST MYCOBACTERIUM TUBERCULOSIS BY THE POPULATION OF REGULATORY DENDRITIC CELLS2220-76192313-739810.15789/2220-7619-2018-2-169-174https://doaj.org/article/4465056cbbb64025949644f0f30876ee2018-09-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/735https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398On 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.E. I. RubakovaM. A. KapinaN. N. LogunovaK. B. MajorovA. S. AptSankt-Peterburg : NIIÈM imeni Pasteraarticledcregtregtuberculosisexperimental modellung pathologyInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 8, Iss 2, Pp 169-174 (2018)
institution	DOAJ
collection	DOAJ
language	RU
topic	dcreg treg tuberculosis experimental model lung pathology Infectious and parasitic diseases RC109-216
spellingShingle	dcreg treg tuberculosis experimental model lung pathology Infectious and parasitic diseases RC109-216 E. I. Rubakova M. A. Kapina N. N. Logunova K. B. Majorov A. S. Apt REGULATION OF IMMUNE RESPONSE AGAINST MYCOBACTERIUM TUBERCULOSIS BY THE POPULATION OF REGULATORY DENDRITIC CELLS
description	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.
format	article
author	E. I. Rubakova M. A. Kapina N. N. Logunova K. B. Majorov A. S. Apt
author_facet	E. I. Rubakova M. A. Kapina N. N. Logunova K. B. Majorov A. S. Apt
author_sort	E. I. Rubakova
title	REGULATION OF IMMUNE RESPONSE AGAINST MYCOBACTERIUM TUBERCULOSIS BY THE POPULATION OF REGULATORY DENDRITIC CELLS
title_short	REGULATION OF IMMUNE RESPONSE AGAINST MYCOBACTERIUM TUBERCULOSIS BY THE POPULATION OF REGULATORY DENDRITIC CELLS
title_full	REGULATION OF IMMUNE RESPONSE AGAINST MYCOBACTERIUM TUBERCULOSIS BY THE POPULATION OF REGULATORY DENDRITIC CELLS
title_fullStr	REGULATION OF IMMUNE RESPONSE AGAINST MYCOBACTERIUM TUBERCULOSIS BY THE POPULATION OF REGULATORY DENDRITIC CELLS
title_full_unstemmed	REGULATION OF IMMUNE RESPONSE AGAINST MYCOBACTERIUM TUBERCULOSIS BY THE POPULATION OF REGULATORY DENDRITIC CELLS
title_sort	regulation of immune response against mycobacterium tuberculosis by the population of regulatory dendritic cells
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2018
url	https://doaj.org/article/4465056cbbb64025949644f0f30876ee
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_version_	1718417973003157504

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

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