Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.

Suppressor of cytokine signalling 3 (SOCS3) negatively regulates STAT3 activation in response to several cytokines such as those in the gp130-containing IL-6 receptor family. Thus, SOCS3 may play a major role in immune responses to pathogens. In the present study, the role of SOCS3 in M. tuberculosi...

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Autores principales:	Berit Carow, Ann-Kathrin Reuschl, Dolores Gavier-Widén, Brendan J Jenkins, Matthias Ernst, Akihiko Yoshimura, Benedict J Chambers, Martin E Rottenberg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ccb20071a27346fea8f7fc0ef60e5438
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spelling	oai:doaj.org-article:ccb20071a27346fea8f7fc0ef60e54382021-11-18T06:05:26ZCritical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.1553-73661553-737410.1371/journal.ppat.1003442https://doaj.org/article/ccb20071a27346fea8f7fc0ef60e54382013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23853585/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Suppressor of cytokine signalling 3 (SOCS3) negatively regulates STAT3 activation in response to several cytokines such as those in the gp130-containing IL-6 receptor family. Thus, SOCS3 may play a major role in immune responses to pathogens. In the present study, the role of SOCS3 in M. tuberculosis infection was examined. All Socs3(fl/fl) LysM cre, Socs3(fl/fl) lck cre (with SOCS3-deficient myeloid and lymphoid cells, respectively) and gp130(F/F) mice, with a mutation in gp130 that impedes binding to SOCS3, showed increased susceptibility to infection with M. tuberculosis. SOCS3 binding to gp130 in myeloid cells conveyed resistance to M. tuberculosis infection via the regulation of IL-6/STAT3 signalling. SOCS3 was redundant for mycobacterial control by macrophages in vitro. Instead, SOCS3 expression in infected macrophages and DCs prevented the IL-6-mediated inhibition of TNF and IL-12 secretion and contributed to a timely CD4+ cell-dependent IFN-γ expression in vivo. In T cells, SOCS3 expression was essential for a gp130-independent control of infection with M. tuberculosis, but was neither required for the control of infection with attenuated M. bovis BCG nor for M. tuberculosis in BCG-vaccinated mice. Socs3(fl/fl) lck cre mice showed an increased frequency of γδ+ T cells in different organs and an enhanced secretion of IL-17 by γδ+ T cells in response to infection. Socs3(fl/fl) lck cre γδ+ T cells impaired the control of infection with M. tuberculosis. Thus, SOCS3 expression in either lymphoid or myeloid cells is essential for resistance against M. tuberculosis via discrete mechanisms.Berit CarowAnn-Kathrin ReuschlDolores Gavier-WidénBrendan J JenkinsMatthias ErnstAkihiko YoshimuraBenedict J ChambersMartin E RottenbergPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 7, p e1003442 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Berit Carow Ann-Kathrin Reuschl Dolores Gavier-Widén Brendan J Jenkins Matthias Ernst Akihiko Yoshimura Benedict J Chambers Martin E Rottenberg Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.
description	Suppressor of cytokine signalling 3 (SOCS3) negatively regulates STAT3 activation in response to several cytokines such as those in the gp130-containing IL-6 receptor family. Thus, SOCS3 may play a major role in immune responses to pathogens. In the present study, the role of SOCS3 in M. tuberculosis infection was examined. All Socs3(fl/fl) LysM cre, Socs3(fl/fl) lck cre (with SOCS3-deficient myeloid and lymphoid cells, respectively) and gp130(F/F) mice, with a mutation in gp130 that impedes binding to SOCS3, showed increased susceptibility to infection with M. tuberculosis. SOCS3 binding to gp130 in myeloid cells conveyed resistance to M. tuberculosis infection via the regulation of IL-6/STAT3 signalling. SOCS3 was redundant for mycobacterial control by macrophages in vitro. Instead, SOCS3 expression in infected macrophages and DCs prevented the IL-6-mediated inhibition of TNF and IL-12 secretion and contributed to a timely CD4+ cell-dependent IFN-γ expression in vivo. In T cells, SOCS3 expression was essential for a gp130-independent control of infection with M. tuberculosis, but was neither required for the control of infection with attenuated M. bovis BCG nor for M. tuberculosis in BCG-vaccinated mice. Socs3(fl/fl) lck cre mice showed an increased frequency of γδ+ T cells in different organs and an enhanced secretion of IL-17 by γδ+ T cells in response to infection. Socs3(fl/fl) lck cre γδ+ T cells impaired the control of infection with M. tuberculosis. Thus, SOCS3 expression in either lymphoid or myeloid cells is essential for resistance against M. tuberculosis via discrete mechanisms.
format	article
author	Berit Carow Ann-Kathrin Reuschl Dolores Gavier-Widén Brendan J Jenkins Matthias Ernst Akihiko Yoshimura Benedict J Chambers Martin E Rottenberg
author_facet	Berit Carow Ann-Kathrin Reuschl Dolores Gavier-Widén Brendan J Jenkins Matthias Ernst Akihiko Yoshimura Benedict J Chambers Martin E Rottenberg
author_sort	Berit Carow
title	Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.
title_short	Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.
title_full	Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.
title_fullStr	Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.
title_full_unstemmed	Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.
title_sort	critical and independent role for socs3 in either myeloid or t cells in resistance to mycobacterium tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ccb20071a27346fea8f7fc0ef60e5438
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Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.

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