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"
Altmetric
Citation Impact
MSK Authors
  1. Eric Pamer
    277 Pamer
  2. Ingrid Leiner
    49 Leiner
  3. Jesse Coward
    14 Coward
  4. Nancy Collins
    82 Collins