Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation Journal Article
| Authors: | Rivera, A.; Hohl, T. M.; Collins, N.; Leiner, I.; Gallegos, A.; Saijo, S.; Coward, J. W.; Iwakura, Y.; Pamer, E. G. |
| Article Title: | Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation |
| 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. © 2011 Rivera et al. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 208 |
| Issue: | 2 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2011-02-14 |
| Start Page: | 369 |
| End Page: | 381 |
| Language: | English |
| DOI: | 10.1084/jem.20100906 |
| PROVIDER: | scopus |
| PMCID: | PMC3039849 |
| PUBMED: | 21242294 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 March 2011" - "CODEN: JEMEA" - "Source: Scopus" |
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