Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection

Matthew J Robinson, Fabiola Osorio, Marcela Rosas, Rui P Freitas, Edina Schweighoffer, Olaf Gross, J Sjef Verbeek, Jürgen Ruland, Victor Tybulewicz, Gordon D Brown, Luis Ferreira Moita, Philip R Taylor, Caetano Reis e Sousa

Research output: Contribution to journalArticlepeer-review

320 Citations (Scopus)

Abstract

Innate immune cells detect pathogens via pattern recognition receptors (PRRs), which signal for initiation of immune responses to infection. Studies with Dectin-1, a PRR for fungi, have defined a novel innate signaling pathway involving Syk kinase and the adaptor CARD9, which is critical for inducing Th17 responses to fungal infection. We show that another C-type lectin, Dectin-2, also signals via Syk and CARD9, and contributes to dendritic cell (DC) activation by fungal particles. Unlike Dectin-1, Dectin-2 couples to Syk indirectly, through association with the FcRgamma chain. In a model of Candida albicans infection, blockade of Dectin-2 did not affect innate immune resistance but abrogated Candida-specific T cell production of IL-17 and, in combination with the absence of Dectin-1, decreased Th1 responses to the organism. Thus, Dectin-2 constitutes a major fungal PRR that can couple to the Syk-CARD9 innate signaling pathway to activate DCs and regulate adaptive immune responses to fungal infection.
Original languageEnglish
Pages (from-to)2037-2051
Number of pages15
JournalJournal of Experimental Medicine
Volume206
Issue number9
DOIs
Publication statusPublished - 31 Aug 2009

Keywords

  • adaptor proteins, signal transducing
  • adaptor proteins, vesicular transport
  • animals
  • candidiasis
  • flow cytometry
  • immunoblotting
  • interleukin-17
  • intracellular signaling peptides and proteins
  • lectins, C-type
  • mice
  • mice, inbred C57BL
  • mice, knockout
  • myeloid differentiation factor 88
  • protein-tyrosine kinases
  • receptors, pattern recognition
  • reverse transcriptase polymerase chain reaction
  • signal transduction
  • t-lymphocytes, helper-inducer

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