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 journalArticle

316 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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  • Cite this

    Robinson, M. J., Osorio, F., Rosas, M., Freitas, R. P., Schweighoffer, E., Gross, O., Verbeek, J. S., Ruland, J., Tybulewicz, V., Brown, G. D., Moita, L. F., Taylor, P. R., & Reis e Sousa, C. (2009). Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. Journal of Experimental Medicine, 206(9), 2037-2051. https://doi.org/10.1084/jem.20082818