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BMC Immunology
Published in: BMC Immunology 1/2014

Open Access 01-12-2014 | Research article

Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene

Authors: Mathieu Goupil, Vincent Cousineau-Côté, Francine Aumont, Serge Sénéchal, Louis Gaboury, Zaher Hanna, Paul Jolicoeur, Louis de Repentigny

Published in: BMC Immunology | Issue 1/2014

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Abstract

Background

The tissue-signaling cytokines IL-17 and IL-22 are critical to host defense against oral Candida albicans infection, by their induction of oral antimicrobial peptide expression and recruitment of neutrophils. Mucosal Th17 cells which produce these cytokines are preferentially depleted in HIV-infected patients. Here, we tested the hypothesis that defective IL-17- and IL-22-dependent host responses to C. albicans determine the phenotype of susceptibility to oropharyngeal candidiasis (OPC) in transgenic (Tg) mice expressing HIV-1.

Results

Naïve CD4+ T-cells and the differentiated Th1, Th2, Th17, Th1Th17 and Treg lineages were all profoundly depleted in cervical lymph nodes (CLNs) of these Tg mice. However, naive CD4+ cells from Tg mice maintained the capacity to differentiate into these lineages in response to polarizing cytokines in vitro. Expression of Il17, Il22, S100a8 and Ccl20 was enhanced in oral mucosal tissue of non-Tg, but not of Tg mice, after oral infection with C. albicans. Treatment of infected Tg mice with the combination of IL-17 and IL-22, but not IL-17 or Il-22 alone, significantly reduced oral burdens of C. albicans and abundance of Candida hyphae in the epithelium of tongues of infected Tg mice, and restored the ability of the Tg mice to up-regulate expression of S100a8 and Ccl20 in response to C. albicans infection.

Conclusions

These findings demonstrate that defective IL-17- and IL-22-dependent induction of innate mucosal immunity to C. albicans is central to the phenotype of susceptibility to OPC in these HIV transgenic mice.
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Metadata
Title
Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene
Authors
Mathieu Goupil
Vincent Cousineau-Côté
Francine Aumont
Serge Sénéchal
Louis Gaboury
Zaher Hanna
Paul Jolicoeur
Louis de Repentigny
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2014
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-014-0049-9

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