Fonsecaea pedrosoi-induced Th17-cell differentiation in mice is fostered by Dectin-2 and suppressed by Mincle recognition.

Abstract

Chromoblastomycosis is a chronic skin infection caused by the pigmented saprophytic mould Fonsecaea pedrosoi. Chronicity of infection can be broken by a coordinated innate recognition of the spores by pattern recognition receptors. While Mincle signaling via the Syk/Card9 pathway is required for fungal recognition by host cells, it is not sufficient for host control. Exogenously applied TLR agonists are necessary to promote the induction of proinflammatory cytokines and clearance of infection in vivo. Here, we investigated whether costimulation by TLR agonists fosters the development of adaptive immune responses, by examining the development of fungus-specific T cells. Subcutaneous infection of mice with F. pedrosoi spores induced the activation, expansion, and differentiation of Ag-specific CD4(+) T cells but TLR costimulation did not further augment these T-cell responses. The Dectin-2/FcRγ/Card9 signaling pathway promoted the differentiation of fungus-specific CD4(+) T cells into Th17 cells, whereas Mincle inhibited the development of this T-helper subset in infected mice. These results indicate differential roles for Dectin-2 and Mincle in the generation of adaptive immune responses to F. pedrosoi infection.

• Authors: Marcel Wüthrich, Huafeng Wang, Mengyi Li, Tassanee Lerksuthirat, Sarah E Hardison, Gordon D Brown, Bruce Klein
• Journal: European journal of immunology (Eur J Immunol) Vol. 45 Issue 9 Pg. 2542-52 (Sep 2015) ISSN: 1521-4141 [Electronic] Germany
• PMID: 26140582 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• CARD Signaling Adaptor Proteins
• Card9 protein, mouse
• Clecsf8 protein, mouse
• Intracellular Signaling Peptides and Proteins
• Lectins, C-Type
• Membrane Proteins
• Receptors, IgG
• dectin-2, mouse
• Protein-Tyrosine Kinases
• Syk Kinase
• Syk protein, mouse

Topics

• Adaptive Immunity
• Animals
• CARD Signaling Adaptor Proteins (genetics, immunology)
• Cell Differentiation
• Chromoblastomycosis (immunology, microbiology, pathology)
• Gene Expression Regulation
• Host-Pathogen Interactions
• Injections, Subcutaneous
• Intracellular Signaling Peptides and Proteins (genetics, immunology)
• Lectins, C-Type (genetics, immunology)
• Membrane Proteins (genetics, immunology)
• Mice
• Mice, Transgenic
• Protein-Tyrosine Kinases (genetics, immunology)
• Receptors, IgG (genetics, immunology)
• Saccharomycetales (immunology, pathogenicity)
• Signal Transduction
• Skin (immunology, microbiology, pathology)
• Spores, Fungal (immunology, pathogenicity)
• Syk Kinase
• Th17 Cells (immunology, microbiology, pathology)