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Early IL-10 promotes vasculature-associated CD4(+) T cells unable to control Mycobacterium tuberculosis infection

Cytokine-producing CD4(+) T cells play a crucial role in the control of Mycobacterium tuberculosis infection; however, there is a delayed appearance of effector T cells in the lungs following aerosol infection. The immunomodulatory cytokine IL-10 antagonizes control of M. tuberculosis infection thro...

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Autores principales: Ferreira, Catarina M., Barbosa, Ana Margarida, Barreira-Silva, Palmira, Silvestre, Ricardo, Cunha, Cristina, Carvalho, Agostinho, Rodrigues, Fernando, Correia-Neves, Margarida, Castro, António G., Torrado, Egídio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663558/
https://www.ncbi.nlm.nih.gov/pubmed/34554927
http://dx.doi.org/10.1172/jci.insight.150060
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author Ferreira, Catarina M.
Barbosa, Ana Margarida
Barreira-Silva, Palmira
Silvestre, Ricardo
Cunha, Cristina
Carvalho, Agostinho
Rodrigues, Fernando
Correia-Neves, Margarida
Castro, António G.
Torrado, Egídio
author_facet Ferreira, Catarina M.
Barbosa, Ana Margarida
Barreira-Silva, Palmira
Silvestre, Ricardo
Cunha, Cristina
Carvalho, Agostinho
Rodrigues, Fernando
Correia-Neves, Margarida
Castro, António G.
Torrado, Egídio
author_sort Ferreira, Catarina M.
collection PubMed
description Cytokine-producing CD4(+) T cells play a crucial role in the control of Mycobacterium tuberculosis infection; however, there is a delayed appearance of effector T cells in the lungs following aerosol infection. The immunomodulatory cytokine IL-10 antagonizes control of M. tuberculosis infection through mechanisms associated with reduced CD4(+) T cell responses. Here, we show that IL-10 overexpression only before the onset of the T cell response impaired control of M. tuberculosis growth; during chronic infection, IL-10 overexpression reduced the CD4(+) T cell response without affecting the outcome of infection. IL-10 overexpression early during infection did not, we found, significantly impair the kinetics of CD4(+) T cell priming and effector differentiation. However, CD4(+) T cells primed and differentiated in an IL-10–enriched environment displayed reduced expression of CXCR3 and, because they did not migrate into the lung parenchyma, their ability to control infection was limited. Importantly, these CD4(+) T cells maintained their vasculature phenotype and were unable to control infection, even after adoptive transfer into low IL-10 settings. Together our data support a model wherein, during M. tuberculosis infection, IL-10 acts intrinsically on T cells, impairing their parenchymal migratory capacity and ability to engage with infected phagocytic cells, thereby impeding control of infection.
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spelling pubmed-86635582021-12-15 Early IL-10 promotes vasculature-associated CD4(+) T cells unable to control Mycobacterium tuberculosis infection Ferreira, Catarina M. Barbosa, Ana Margarida Barreira-Silva, Palmira Silvestre, Ricardo Cunha, Cristina Carvalho, Agostinho Rodrigues, Fernando Correia-Neves, Margarida Castro, António G. Torrado, Egídio JCI Insight Research Article Cytokine-producing CD4(+) T cells play a crucial role in the control of Mycobacterium tuberculosis infection; however, there is a delayed appearance of effector T cells in the lungs following aerosol infection. The immunomodulatory cytokine IL-10 antagonizes control of M. tuberculosis infection through mechanisms associated with reduced CD4(+) T cell responses. Here, we show that IL-10 overexpression only before the onset of the T cell response impaired control of M. tuberculosis growth; during chronic infection, IL-10 overexpression reduced the CD4(+) T cell response without affecting the outcome of infection. IL-10 overexpression early during infection did not, we found, significantly impair the kinetics of CD4(+) T cell priming and effector differentiation. However, CD4(+) T cells primed and differentiated in an IL-10–enriched environment displayed reduced expression of CXCR3 and, because they did not migrate into the lung parenchyma, their ability to control infection was limited. Importantly, these CD4(+) T cells maintained their vasculature phenotype and were unable to control infection, even after adoptive transfer into low IL-10 settings. Together our data support a model wherein, during M. tuberculosis infection, IL-10 acts intrinsically on T cells, impairing their parenchymal migratory capacity and ability to engage with infected phagocytic cells, thereby impeding control of infection. American Society for Clinical Investigation 2021-11-08 /pmc/articles/PMC8663558/ /pubmed/34554927 http://dx.doi.org/10.1172/jci.insight.150060 Text en © 2021 Ferreira et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Ferreira, Catarina M.
Barbosa, Ana Margarida
Barreira-Silva, Palmira
Silvestre, Ricardo
Cunha, Cristina
Carvalho, Agostinho
Rodrigues, Fernando
Correia-Neves, Margarida
Castro, António G.
Torrado, Egídio
Early IL-10 promotes vasculature-associated CD4(+) T cells unable to control Mycobacterium tuberculosis infection
title Early IL-10 promotes vasculature-associated CD4(+) T cells unable to control Mycobacterium tuberculosis infection
title_full Early IL-10 promotes vasculature-associated CD4(+) T cells unable to control Mycobacterium tuberculosis infection
title_fullStr Early IL-10 promotes vasculature-associated CD4(+) T cells unable to control Mycobacterium tuberculosis infection
title_full_unstemmed Early IL-10 promotes vasculature-associated CD4(+) T cells unable to control Mycobacterium tuberculosis infection
title_short Early IL-10 promotes vasculature-associated CD4(+) T cells unable to control Mycobacterium tuberculosis infection
title_sort early il-10 promotes vasculature-associated cd4(+) t cells unable to control mycobacterium tuberculosis infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663558/
https://www.ncbi.nlm.nih.gov/pubmed/34554927
http://dx.doi.org/10.1172/jci.insight.150060
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