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Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment

BACKGROUND: Recent advances demonstrated that liver dendritic cells (DCs) promote immunologic hyporesponsiveness that may contribute to hepatic tolerance. Although there has been significant work on the phenotypic and functional roles of such DCs, the impact of liver microenvironment on the immune p...

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Autores principales: Donaghy, Ludovic, Cabillic, Florian, Corlu, Anne, Rostan, Octavie, Toutirais, Olivier, Guguen-Guillouzo, Christiane, Guiguen, Claude, Gangneux, Jean-Pierre
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882335/
https://www.ncbi.nlm.nih.gov/pubmed/20544029
http://dx.doi.org/10.1371/journal.pntd.0000703
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author Donaghy, Ludovic
Cabillic, Florian
Corlu, Anne
Rostan, Octavie
Toutirais, Olivier
Guguen-Guillouzo, Christiane
Guiguen, Claude
Gangneux, Jean-Pierre
author_facet Donaghy, Ludovic
Cabillic, Florian
Corlu, Anne
Rostan, Octavie
Toutirais, Olivier
Guguen-Guillouzo, Christiane
Guiguen, Claude
Gangneux, Jean-Pierre
author_sort Donaghy, Ludovic
collection PubMed
description BACKGROUND: Recent advances demonstrated that liver dendritic cells (DCs) promote immunologic hyporesponsiveness that may contribute to hepatic tolerance. Although there has been significant work on the phenotypic and functional roles of such DCs, the impact of liver microenvironment on the immune properties of infected DC is still poorly explored, probably because of the limitations of modelization. METHODOLOGY/PRINCIPAL FINDINGS: Here, we hypothesized that DC tolerogenic properties have an impact on the antimicrobial response, particularly during the infection by the protozoan parasite Leishmania donovani. Indeed, a lymphocytic Th2 environment was reported to favour the growth and proliferation of L. donovani. We first modelized an adequate monocyte-differentiated DC model, either in rat liver epithelial cell- or in a human hepatic non-parenchymal cell-conditioned medium in order to infect them further. We established that DCs differentiated in a hepatic microenvironment displayed a CD14+/CD16+/CD123+ phenotype, secreted low IL-12p70 and had an impaired capacity to stimulate allogeneic T lymphocyte proliferation and IFNγ secretion. We then infected DCs with L. donovani in the in vitro-defined hepatic microenvironment. The infection of hepatic DCs restored their capacity to stimulate allogeneic T-cell proliferation and to induce lymphocytic secretion of IFNγ. Such characteristics were recently shown to favour granuloma formation in mice liver. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the specific immunostimulatory properties of infected hepatic DCs might amplify the granuloma maturation, which warrants the effective control of infection in the liver during visceral leishmaniasis.
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spelling pubmed-28823352010-06-11 Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment Donaghy, Ludovic Cabillic, Florian Corlu, Anne Rostan, Octavie Toutirais, Olivier Guguen-Guillouzo, Christiane Guiguen, Claude Gangneux, Jean-Pierre PLoS Negl Trop Dis Research Article BACKGROUND: Recent advances demonstrated that liver dendritic cells (DCs) promote immunologic hyporesponsiveness that may contribute to hepatic tolerance. Although there has been significant work on the phenotypic and functional roles of such DCs, the impact of liver microenvironment on the immune properties of infected DC is still poorly explored, probably because of the limitations of modelization. METHODOLOGY/PRINCIPAL FINDINGS: Here, we hypothesized that DC tolerogenic properties have an impact on the antimicrobial response, particularly during the infection by the protozoan parasite Leishmania donovani. Indeed, a lymphocytic Th2 environment was reported to favour the growth and proliferation of L. donovani. We first modelized an adequate monocyte-differentiated DC model, either in rat liver epithelial cell- or in a human hepatic non-parenchymal cell-conditioned medium in order to infect them further. We established that DCs differentiated in a hepatic microenvironment displayed a CD14+/CD16+/CD123+ phenotype, secreted low IL-12p70 and had an impaired capacity to stimulate allogeneic T lymphocyte proliferation and IFNγ secretion. We then infected DCs with L. donovani in the in vitro-defined hepatic microenvironment. The infection of hepatic DCs restored their capacity to stimulate allogeneic T-cell proliferation and to induce lymphocytic secretion of IFNγ. Such characteristics were recently shown to favour granuloma formation in mice liver. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the specific immunostimulatory properties of infected hepatic DCs might amplify the granuloma maturation, which warrants the effective control of infection in the liver during visceral leishmaniasis. Public Library of Science 2010-06-08 /pmc/articles/PMC2882335/ /pubmed/20544029 http://dx.doi.org/10.1371/journal.pntd.0000703 Text en Donaghy 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
Donaghy, Ludovic
Cabillic, Florian
Corlu, Anne
Rostan, Octavie
Toutirais, Olivier
Guguen-Guillouzo, Christiane
Guiguen, Claude
Gangneux, Jean-Pierre
Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment
title Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment
title_full Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment
title_fullStr Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment
title_full_unstemmed Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment
title_short Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment
title_sort immunostimulatory properties of dendritic cells after leishmania donovani infection using an in vitro model of liver microenvironment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882335/
https://www.ncbi.nlm.nih.gov/pubmed/20544029
http://dx.doi.org/10.1371/journal.pntd.0000703
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