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IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis
IL-10 is a critical regulatory cytokine involved in the pathogenesis of visceral leishmaniasis caused by Leishmania donovani and clinical and experimental data indicate that disease progression is associated with expanded numbers of CD4(+) IFNγ(+) T cells committed to IL-10 production. Here, combini...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406093/ https://www.ncbi.nlm.nih.gov/pubmed/22911108 http://dx.doi.org/10.1371/journal.ppat.1002827 |
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author | Owens, Benjamin M. J. Beattie, Lynette Moore, John W. J. Brown, Najmeeyah Mann, Jason L. Dalton, Jane E. Maroof, Asher Kaye, Paul M. |
author_facet | Owens, Benjamin M. J. Beattie, Lynette Moore, John W. J. Brown, Najmeeyah Mann, Jason L. Dalton, Jane E. Maroof, Asher Kaye, Paul M. |
author_sort | Owens, Benjamin M. J. |
collection | PubMed |
description | IL-10 is a critical regulatory cytokine involved in the pathogenesis of visceral leishmaniasis caused by Leishmania donovani and clinical and experimental data indicate that disease progression is associated with expanded numbers of CD4(+) IFNγ(+) T cells committed to IL-10 production. Here, combining conditional cell-specific depletion with adoptive transfer, we demonstrate that only conventional CD11c(hi) DCs that produce both IL-10 and IL-27 are capable of inducing IL-10-producing Th1 cells in vivo. In contrast, CD11c(hi) as well as CD11c(int/lo) cells isolated from infected mice were capable of reversing the host protective effect of diphtheria toxin-mediated CD11c(+) cell depletion. This was reflected by increased splenomegaly, inhibition of NO production and increased parasite burden. Thus during chronic infection, multiple CD11c(+) cell populations can actively suppress host resistance and enhance immunopathology, through mechanisms that do not necessarily involve IL-10-producing Th1 cells. |
format | Online Article Text |
id | pubmed-3406093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34060932012-07-30 IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis Owens, Benjamin M. J. Beattie, Lynette Moore, John W. J. Brown, Najmeeyah Mann, Jason L. Dalton, Jane E. Maroof, Asher Kaye, Paul M. PLoS Pathog Research Article IL-10 is a critical regulatory cytokine involved in the pathogenesis of visceral leishmaniasis caused by Leishmania donovani and clinical and experimental data indicate that disease progression is associated with expanded numbers of CD4(+) IFNγ(+) T cells committed to IL-10 production. Here, combining conditional cell-specific depletion with adoptive transfer, we demonstrate that only conventional CD11c(hi) DCs that produce both IL-10 and IL-27 are capable of inducing IL-10-producing Th1 cells in vivo. In contrast, CD11c(hi) as well as CD11c(int/lo) cells isolated from infected mice were capable of reversing the host protective effect of diphtheria toxin-mediated CD11c(+) cell depletion. This was reflected by increased splenomegaly, inhibition of NO production and increased parasite burden. Thus during chronic infection, multiple CD11c(+) cell populations can actively suppress host resistance and enhance immunopathology, through mechanisms that do not necessarily involve IL-10-producing Th1 cells. Public Library of Science 2012-07-26 /pmc/articles/PMC3406093/ /pubmed/22911108 http://dx.doi.org/10.1371/journal.ppat.1002827 Text en Owens et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Owens, Benjamin M. J. Beattie, Lynette Moore, John W. J. Brown, Najmeeyah Mann, Jason L. Dalton, Jane E. Maroof, Asher Kaye, Paul M. IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis |
title | IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis |
title_full | IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis |
title_fullStr | IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis |
title_full_unstemmed | IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis |
title_short | IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis |
title_sort | il-10-producing th1 cells and disease progression are regulated by distinct cd11c(+) cell populations during visceral leishmaniasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406093/ https://www.ncbi.nlm.nih.gov/pubmed/22911108 http://dx.doi.org/10.1371/journal.ppat.1002827 |
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