Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc.

Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. Research Abstract Details 

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Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. Abstract Text:

Antonella De Luca,Claudia Montagnoli,Teresa Zelante,Pierluigi Bonifazi,Silvia Bozza,Silvia Moretti,Carmen D'Angelo,Carmine Vacca,Louis Boon,Francesco Bistoni,Paolo Puccetti,Francesca Fallarino,Luigina Romani,Antonella De Luca,Claudia Montagnoli,Teresa Zelante,Pierluigi Bonifazi,Silvia Bozza,Silvia Moretti,Carmen D'Angelo,Carmine Vacca,Louis Boon,Francesco Bistoni,Paolo Puccetti,Francesca Fallarino,Luigina Romani,

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 RORgammat, 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 RORgammat-expressing T cells.

Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. Publishing Authors By Initials

A De Luca,C Montagnoli,T Zelante,P Bonifazi,S Bozza,S Moretti,C D'Angelo,C Vacca,L Boon,F Bistoni,P Puccetti,F Fallarino,L Romani,A De Luca,C Montagnoli,T Zelante,P Bonifazi,S Bozza,S Moretti,C D'Angelo,C Vacca,L Boon,F Bistoni,P Puccetti,F Fallarino,L Romani,

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Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 179

Page Numbers: 5999-6008

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 1

MONTH: Nov

YEAR: 2007

Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. Information

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LANGUAGE: eng

NlmUniqueID: 2985117

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Grant and Affiliation Information for Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc.

AFFILIATION: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.

Country: United States

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MEDLINETA: J Immunol

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