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

Eur J Immunol. 2015 Sep;45(9):2542-52. doi: 10.1002/eji.201545591. Epub 2015 Jul 28.

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.

Keywords: C-type lectin; Chromoblastomycosis; Dectin-2; Fungi; Mincle; T-cell differentiation; Th17 cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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