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Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression

Controlled immune activation in response to commensal microbes is critical for the maintenance of stable colonization and prevention of microbial overgrowth on epithelial surfaces. Our understanding of the host mechanisms that regulate bacterial commensalism has increased substantially, however, muc...

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Autores principales: Kirchner, Florian R., Littringer, Katharina, Altmeier, Simon, Tran, Van Du T., Schönherr, Franziska, Lemberg, Christina, Pagni, Marco, Sanglard, Dominique, Joller, Nicole, LeibundGut-Landmann, Salomé
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400982/
https://www.ncbi.nlm.nih.gov/pubmed/30873177
http://dx.doi.org/10.3389/fimmu.2019.00330
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author Kirchner, Florian R.
Littringer, Katharina
Altmeier, Simon
Tran, Van Du T.
Schönherr, Franziska
Lemberg, Christina
Pagni, Marco
Sanglard, Dominique
Joller, Nicole
LeibundGut-Landmann, Salomé
author_facet Kirchner, Florian R.
Littringer, Katharina
Altmeier, Simon
Tran, Van Du T.
Schönherr, Franziska
Lemberg, Christina
Pagni, Marco
Sanglard, Dominique
Joller, Nicole
LeibundGut-Landmann, Salomé
author_sort Kirchner, Florian R.
collection PubMed
description Controlled immune activation in response to commensal microbes is critical for the maintenance of stable colonization and prevention of microbial overgrowth on epithelial surfaces. Our understanding of the host mechanisms that regulate bacterial commensalism has increased substantially, however, much less data exist regarding host responses to members of the fungal microbiota on colonized surfaces. Using a murine model of oropharyngeal candidiasis, we have recently shown that differences in immune activation in response to diverse natural isolates of Candida albicans are associated with different outcomes of the host-fungal interaction. Here we applied a genome-wide transcriptomic approach to show that rapid induction of a strong inflammatory response characterized by neutrophil-associated genes upon C. albicans colonization inversely correlated with the ability of the fungus to persist in the oral mucosa. Surprisingly, persistent fungal isolates showed no signs of a compensatory regulatory immune response. By combining RNA-seq data, genetic mouse models, and co-infection experiments, we show that attenuation of the inflammatory response at the onset of infection with a persistent isolate is not a consequence of enhanced immunosuppression. Importantly, depletion of regulatory T cells or deletion of the immunoregulatory cytokine IL-10 did not alter host-protective type 17 immunity nor did it impair fungal survival in the oral mucosa, indicating that persistence of C. albicans in the oral mucosa is not a consequence of suppressed antifungal immunity.
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spelling pubmed-64009822019-03-14 Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression Kirchner, Florian R. Littringer, Katharina Altmeier, Simon Tran, Van Du T. Schönherr, Franziska Lemberg, Christina Pagni, Marco Sanglard, Dominique Joller, Nicole LeibundGut-Landmann, Salomé Front Immunol Immunology Controlled immune activation in response to commensal microbes is critical for the maintenance of stable colonization and prevention of microbial overgrowth on epithelial surfaces. Our understanding of the host mechanisms that regulate bacterial commensalism has increased substantially, however, much less data exist regarding host responses to members of the fungal microbiota on colonized surfaces. Using a murine model of oropharyngeal candidiasis, we have recently shown that differences in immune activation in response to diverse natural isolates of Candida albicans are associated with different outcomes of the host-fungal interaction. Here we applied a genome-wide transcriptomic approach to show that rapid induction of a strong inflammatory response characterized by neutrophil-associated genes upon C. albicans colonization inversely correlated with the ability of the fungus to persist in the oral mucosa. Surprisingly, persistent fungal isolates showed no signs of a compensatory regulatory immune response. By combining RNA-seq data, genetic mouse models, and co-infection experiments, we show that attenuation of the inflammatory response at the onset of infection with a persistent isolate is not a consequence of enhanced immunosuppression. Importantly, depletion of regulatory T cells or deletion of the immunoregulatory cytokine IL-10 did not alter host-protective type 17 immunity nor did it impair fungal survival in the oral mucosa, indicating that persistence of C. albicans in the oral mucosa is not a consequence of suppressed antifungal immunity. Frontiers Media S.A. 2019-02-27 /pmc/articles/PMC6400982/ /pubmed/30873177 http://dx.doi.org/10.3389/fimmu.2019.00330 Text en Copyright © 2019 Kirchner, Littringer, Altmeier, Tran, Schönherr, Lemberg, Pagni, Sanglard, Joller and LeibundGut-Landmann. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Kirchner, Florian R.
Littringer, Katharina
Altmeier, Simon
Tran, Van Du T.
Schönherr, Franziska
Lemberg, Christina
Pagni, Marco
Sanglard, Dominique
Joller, Nicole
LeibundGut-Landmann, Salomé
Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression
title Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression
title_full Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression
title_fullStr Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression
title_full_unstemmed Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression
title_short Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression
title_sort persistence of candida albicans in the oral mucosa induces a curbed inflammatory host response that is independent of immunosuppression
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400982/
https://www.ncbi.nlm.nih.gov/pubmed/30873177
http://dx.doi.org/10.3389/fimmu.2019.00330
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