IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract
A significant proportion of individuals develop chronic, persistent and recurrent genital tract infections with Chlamydia trachomatis, which has been attributed to the numerous strategies that the bacterium uses to subvert host immune responses. Animal chlamydia models have demonstrated that protect...
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Frontiers Media S.A.
2019-03-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00356/full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leonardo R. Sanchez Leonardo R. Sanchez Gloria J. Godoy Gloria J. Godoy Melisa Gorosito Serrán Melisa Gorosito Serrán Maria L. Breser Maria L. Breser Facundo Fiocca Vernengo Facundo Fiocca Vernengo Pablo Engel Ruben D. Motrich Ruben D. Motrich Adriana Gruppi Adriana Gruppi Virginia E. Rivero Virginia E. Rivero |
spellingShingle |
Leonardo R. Sanchez Leonardo R. Sanchez Gloria J. Godoy Gloria J. Godoy Melisa Gorosito Serrán Melisa Gorosito Serrán Maria L. Breser Maria L. Breser Facundo Fiocca Vernengo Facundo Fiocca Vernengo Pablo Engel Ruben D. Motrich Ruben D. Motrich Adriana Gruppi Adriana Gruppi Virginia E. Rivero Virginia E. Rivero IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract Frontiers in Immunology Chlamydia trachomatis prostatitis regulatory B cells male genital tract infection IL-10 |
author_facet |
Leonardo R. Sanchez Leonardo R. Sanchez Gloria J. Godoy Gloria J. Godoy Melisa Gorosito Serrán Melisa Gorosito Serrán Maria L. Breser Maria L. Breser Facundo Fiocca Vernengo Facundo Fiocca Vernengo Pablo Engel Ruben D. Motrich Ruben D. Motrich Adriana Gruppi Adriana Gruppi Virginia E. Rivero Virginia E. Rivero |
author_sort |
Leonardo R. Sanchez |
title |
IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract |
title_short |
IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract |
title_full |
IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract |
title_fullStr |
IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract |
title_full_unstemmed |
IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract |
title_sort |
il-10 producing b cells dampen protective t cell response and allow chlamydia muridarum infection of the male genital tract |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-03-01 |
description |
A significant proportion of individuals develop chronic, persistent and recurrent genital tract infections with Chlamydia trachomatis, which has been attributed to the numerous strategies that the bacterium uses to subvert host immune responses. Animal chlamydia models have demonstrated that protective immune response is mediated by CD4+ Th1 cytokine responses. Herein, we demonstrate that early after infecting the male genital tract, C. muridarum triggers the production of IL-10 by splenic and lymph node cells. In addition, C. muridarum triggers IL-6 and TNFα secretion. Data obtained from in vitro and in vivo experiments revealed B cells as the major IL-10 contributors. Indeed, purified B cells produced high amounts of IL-10 and also exhibited enhanced expression of inhibitory molecules such as CD39, PD-L1 and PD1 after C. muridarum stimulation. In vitro experiments performed with sorted cell subsets revealed that Marginal Zone B cells were the main IL-10 producers. In vitro and in vivo studies using TLR-deficient mice indicated that TLR4 signaling pathway was essential for IL-10 production. In addition, in vivo treatments to neutralize IL-10 or deplete B cells indicated that IL-10 and B cells played a significant role in delaying bacterial clearance ability. Moreover, the latter was confirmed by adoptive cell transfer experiments in which the absence of IL-10-producing B cells conferred the host a greater capability to induce Th1 responses and clear the infection. Interestingly, NOD mice, which were the least efficient in clearing the infection, presented much more Marginal Zone B counts and also enhanced TLR4 expression on Marginal Zone B cells when compared to B6 and BALB/c mice. Besides, treatment with antibodies that selectively deplete Marginal Zone B cells rendered mice more capable of inducing enhanced IFNγ responses and clearing the infection. Our findings suggest that B cells play a detrimental role in C. muridarum infection and that activation by innate receptors like TLR4 and IL-10 production by these cells could be used by Chlamydia spp. as a strategy to modulate the immune response establishing chronic infections in susceptible hosts. |
topic |
Chlamydia trachomatis prostatitis regulatory B cells male genital tract infection IL-10 |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00356/full |
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doaj-c3d6a144a14f4e5289f02b478640e7f62020-11-24T20:52:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00356445565IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital TractLeonardo R. Sanchez0Leonardo R. Sanchez1Gloria J. Godoy2Gloria J. Godoy3Melisa Gorosito Serrán4Melisa Gorosito Serrán5Maria L. Breser6Maria L. Breser7Facundo Fiocca Vernengo8Facundo Fiocca Vernengo9Pablo Engel10Ruben D. Motrich11Ruben D. Motrich12Adriana Gruppi13Adriana Gruppi14Virginia E. Rivero15Virginia E. Rivero16Centro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaImmunology Unit, Department of Biomedical Sciences, Immunology and Neurosciences, Medical School, University of Barcelona, Barcelona, SpainCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaA significant proportion of individuals develop chronic, persistent and recurrent genital tract infections with Chlamydia trachomatis, which has been attributed to the numerous strategies that the bacterium uses to subvert host immune responses. Animal chlamydia models have demonstrated that protective immune response is mediated by CD4+ Th1 cytokine responses. Herein, we demonstrate that early after infecting the male genital tract, C. muridarum triggers the production of IL-10 by splenic and lymph node cells. In addition, C. muridarum triggers IL-6 and TNFα secretion. Data obtained from in vitro and in vivo experiments revealed B cells as the major IL-10 contributors. Indeed, purified B cells produced high amounts of IL-10 and also exhibited enhanced expression of inhibitory molecules such as CD39, PD-L1 and PD1 after C. muridarum stimulation. In vitro experiments performed with sorted cell subsets revealed that Marginal Zone B cells were the main IL-10 producers. In vitro and in vivo studies using TLR-deficient mice indicated that TLR4 signaling pathway was essential for IL-10 production. In addition, in vivo treatments to neutralize IL-10 or deplete B cells indicated that IL-10 and B cells played a significant role in delaying bacterial clearance ability. Moreover, the latter was confirmed by adoptive cell transfer experiments in which the absence of IL-10-producing B cells conferred the host a greater capability to induce Th1 responses and clear the infection. Interestingly, NOD mice, which were the least efficient in clearing the infection, presented much more Marginal Zone B counts and also enhanced TLR4 expression on Marginal Zone B cells when compared to B6 and BALB/c mice. Besides, treatment with antibodies that selectively deplete Marginal Zone B cells rendered mice more capable of inducing enhanced IFNγ responses and clearing the infection. Our findings suggest that B cells play a detrimental role in C. muridarum infection and that activation by innate receptors like TLR4 and IL-10 production by these cells could be used by Chlamydia spp. as a strategy to modulate the immune response establishing chronic infections in susceptible hosts.https://www.frontiersin.org/article/10.3389/fimmu.2019.00356/fullChlamydia trachomatisprostatitisregulatory B cellsmale genital tractinfectionIL-10 |