Dectin-1 diversifies Aspergillus fumigatus–specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation
Open Access
- 17 January 2011
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 208 (2), 369-381
- https://doi.org/10.1084/jem.20100906
Abstract
Pulmonary infection of mice with Aspergillus fumigatus induces concurrent T helper type 1 (Th1) and Th17 responses that depend on Toll-like receptor/MyD88 and Dectin-1, respectively. However, the mechanisms balancing Th1 and Th17 CD4 T cell populations during infection remain incompletely defined. In this study, we show that Dectin-1 deficiency disproportionally increases Th1 responses and decreases Th17 differentiation after A. fumigatus infection. Dectin-1 signaling in A. fumigatus-infected wild-type mice reduces IFN-γ and IL-12p40 expression in the lung, thereby decreasing T-bet expression in responding CD4 T cells and enhancing Th17 responses. Absence of IFN-γ or IL-12p35 in infected mice or T-bet in responding CD4 T cells enhances Th17 differentiation, independent of Dectin-1 expression, in A. fumigatus-infected mice. Transient deletion of monocyte-derived dendritic cells also reduces Th1 and boosts Th17 differentiation of A. fumigatus-specific CD4 T cells. Our findings indicate that Dectin-1-mediated signals alter CD4 T cell responses to fungal infection by decreasing the production of IL-12 and IFN-γ in innate cells, thereby decreasing T-bet expression in A. fumigatus-specific CD4 T cells and enabling Th17 differentiation.Keywords
This publication has 70 references indexed in Scilit:
- Dectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient- and donor-dependent mechanisms of antifungal immunityBlood, 2010
- Generation of pathogenic TH17 cells in the absence of TGF-β signallingNature, 2010
- Indirect Inhibition of Toll-like Receptor and Type I Interferon Responses by ITAM-Coupled Receptors and IntegrinsImmunity, 2010
- Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infectionThe Journal of Experimental Medicine, 2009
- Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cellsNature Immunology, 2007
- Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17Nature Immunology, 2007
- Transforming growth factor-β induces development of the TH17 lineageNature, 2006
- Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cellsNature, 2006
- The Beta-Glucan Receptor Dectin-1 Recognizes Specific Morphologies of Aspergillus fumigatusPLoS Pathogens, 2005
- Aspergillus fumigatus Triggers Inflammatory Responses by Stage-Specific β-Glucan DisplayPLoS Pathogens, 2005