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

305 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

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Pattern Recognition Receptors
Mycoses
C-Type Lectins
Interleukin-17
Adaptive Immunity
Infection
Candida albicans
Candida
Dendritic Cells
Fungi
T-Lymphocytes
mouse dectin-2
dectin 1

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

Cite this

Robinson, M. J., Osorio, F., Rosas, M., Freitas, R. P., Schweighoffer, E., Gross, O., ... 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

Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. / Robinson, Matthew J; Osorio, Fabiola; Rosas, Marcela; Freitas, Rui P; Schweighoffer, Edina; Gross, Olaf; Verbeek, J Sjef; Ruland, Jürgen; Tybulewicz, Victor; Brown, Gordon D; Moita, Luis Ferreira; Taylor, Philip R; Reis e Sousa, Caetano.

In: Journal of Experimental Medicine, Vol. 206, No. 9, 31.08.2009, p. 2037-2051.

Research output: Contribution to journalArticle

Robinson, MJ, Osorio, F, Rosas, M, Freitas, RP, Schweighoffer, E, Gross, O, Verbeek, JS, Ruland, J, Tybulewicz, V, Brown, GD, Moita, LF, Taylor, PR & 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, vol. 206, no. 9, pp. 2037-2051. https://doi.org/10.1084/jem.20082818
Robinson, Matthew J ; Osorio, Fabiola ; Rosas, Marcela ; Freitas, Rui P ; Schweighoffer, Edina ; Gross, Olaf ; Verbeek, J Sjef ; Ruland, Jürgen ; Tybulewicz, Victor ; Brown, Gordon D ; Moita, Luis Ferreira ; Taylor, Philip R ; Reis e Sousa, Caetano. / Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 9. pp. 2037-2051.
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