Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor γ chain to induce innate immune responses

Kota Sato, Xiao Li Yang, Tatsuo Yudate, Jin Sung Chung, Jianming Wu, Kate Luby-Phelps, Robert P. Kimberly, David Underhill, Ponciano D. Cruz, Kiyoshi Ariizumi

Research output: Contribution to journalArticle

292 Citations (Scopus)

Abstract

Antigen presenting cells recognize pathogens via pattern recognition receptors (PRR), which upon ligation transduce intracellular signals that can induce innate immune responses. Because some C-type lectin-like receptors (e.g. dectin-1 and DC-SIGN) were shown to act as PRR for particular microbes, we considered a similar role for dectin-2. Binding assays using soluble dectin-2 receptors showed the extracellular domain to bind preferentially to hyphal (rather than yeast/conidial) components of Candida albicans, Microsporum audouinii, and Trichophyton rubrum. Selective binding for hyphae was also observed using RAW macrophages expressing dectin-2, the ligation of which by hyphae or cross-linking with dectin-2-specific antibody led to protein tyrosine phosphorylation. Because dectin-2 lacks an intracellular signaling motif, we searched for a signal adaptor that permits it to transduce intracellular signals. First, we found that the Fc receptor γ (FcRγ) chain can bind to dectin-2. Second, ligation of dectin-2 on RAW cells induced tyrosine phosphorylation of FcRγ, activation of NF-κB, internalization of a surrogate ligand, and up-regulated secretion of tumor necrosis factor α and interleukin-1 receptor antagonist. Finally, these dectin-2-induced events were blocked by PP2, an inhibitor of Src kinases that are mediators for FcRγ chain-dependent signaling. We conclude that dectin-2 is a PRR for fungi that employs signaling through FcRγ to induce innate immune responses.

Original languageEnglish (US)
Pages (from-to)38854-38866
Number of pages13
JournalJournal of Biological Chemistry
Volume281
Issue number50
DOIs
StatePublished - Dec 15 2006

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Pattern Recognition Receptors
Fc Receptors
Fungi
Innate Immunity
Ligation
Phosphorylation
Hyphae
Tyrosine
C-Type Lectins
Microsporum
mouse dectin-2
Trichophyton
Interleukin-1 Receptors
src-Family Kinases
Candida
Macrophages
Pathogens
Antigen-Presenting Cells
Candida albicans
Yeast

Cite this

Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor γ chain to induce innate immune responses. / Sato, Kota; Yang, Xiao Li; Yudate, Tatsuo; Chung, Jin Sung; Wu, Jianming; Luby-Phelps, Kate; Kimberly, Robert P.; Underhill, David; Cruz, Ponciano D.; Ariizumi, Kiyoshi.

In: Journal of Biological Chemistry, Vol. 281, No. 50, 15.12.2006, p. 38854-38866.

Research output: Contribution to journalArticle

Sato, K, Yang, XL, Yudate, T, Chung, JS, Wu, J, Luby-Phelps, K, Kimberly, RP, Underhill, D, Cruz, PD & Ariizumi, K 2006, 'Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor γ chain to induce innate immune responses', Journal of Biological Chemistry, vol. 281, no. 50, pp. 38854-38866. https://doi.org/10.1074/jbc.M606542200
Sato, Kota ; Yang, Xiao Li ; Yudate, Tatsuo ; Chung, Jin Sung ; Wu, Jianming ; Luby-Phelps, Kate ; Kimberly, Robert P. ; Underhill, David ; Cruz, Ponciano D. ; Ariizumi, Kiyoshi. / Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor γ chain to induce innate immune responses. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 50. pp. 38854-38866.
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AU - Wu, Jianming

AU - Luby-Phelps, Kate

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