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Functional yet Balanced Reactivity to Candida albicans Requires TRIF, MyD88, and IDO-Dependent Inhibition of Rorc

Authors :
Silvia Moretti
Pierluigi Bonifazi
Louis Boon
Claudia Montagnoli
Carmine Vacca
Francesco Bistoni
Carmen D'Angelo
Silvia Bozza
Luigina Romani
Francesca Fallarino
Teresa Zelante
Antonella De Luca
Paolo Puccetti
Source :
The Journal of Immunology. 179:5999-6008
Publication Year :
2007
Publisher :
The American Association of Immunologists, 2007.

Abstract

The ability of regulatory T (Treg) cells to inhibit aspects of innate and adaptive immunity is central to their protective function in fungal infections. In murine candidiasis, CD4+CD25+ Treg cells prevent excessive inflammation but enable fungal persistence in the gastrointestinal tract, which underlies the onset of durable antifungal protection. In this study, we show that fungal growth, inflammatory immunity, and tolerance to the fungus were all controlled by the coordinate activation of naturally occurring Treg cells, which limited early inflammation at the sites of infection, and pathogen-induced Treg cells (that regulated the expression of adaptive Th immunity in secondary lymphoid organs). Naturally occurring Treg cells required the TRIF pathway for migration to inflamed sites, where the MyD88 pathway would then restrain their suppressive function. Subsequent inflammatory Th1-type immunity was modulated by induced Treg cells, which required the TRIF pathway as well, and acted through activation of IDO in dendritic cells and Th17 cell antagonism. In vitro, using naive CD4+ cells from TRIF-deficient mice, tryptophan metabolites were capable of inducing the Foxp3-encoding gene transcriptionally and suppressing the gene encoding RORγt, Th17 lineage specification factor. This is the first study to show that the same tryptophan catabolites can foster dendritic cell-supported generation of Foxp3+ cells and mediate, at the same time, inhibition of RORγt-expressing T cells.

Details

ISSN :
15506606 and 00221767
Volume :
179
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi.dedup.....967af06b186baa902d687ec2a4a58592
Full Text :
https://doi.org/10.4049/jimmunol.179.9.5999