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Functional yet Balanced Reactivity to Candida albicans Requires TRIF, MyD88, and IDO-Dependent Inhibition of Rorc
- 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.
- Subjects :
- Immunology
chemical and pharmacologic phenomena
Inflammation
Biology
Lymphocyte Activation
T-Lymphocytes, Regulatory
Mice
Immunity
RAR-related orphan receptor gamma
Candida albicans
medicine
Animals
Indoleamine-Pyrrole 2,3,-Dioxygenase
Immunology and Allergy
IL-2 receptor
Mice, Knockout
FOXP3
hemic and immune systems
Dendritic Cells
T-Lymphocytes, Helper-Inducer
Nuclear Receptor Subfamily 1, Group F, Member 3
Acquired immune system
Mice, Inbred C57BL
Adaptor Proteins, Vesicular Transport
TRIF
Myeloid Differentiation Factor 88
Receptors, Opioid
Female
medicine.symptom
Signal transduction
Signal Transduction
Subjects
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