title: Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses.
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 DCSIGN) 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 gamma (FcRgamma) chain can bind to dectin-2. Second, ligation of dectin-2 on RAW cells induced tyrosine phosphorylation of FcRgamma, activation of NF-kappaB, internalization of a surrogate ligand, and up-regulated secretion of tumor necrosis factor alpha and interleukin-1 receptor antagonist. Finally, these dectin-2-induced events were blocked by PP2, an inhibitor of Src kinases that are mediators for FcRgamma chain-dependent signaling. We conclude that dectin-2 is a PRR for fungi that employs signaling through FcRgamma to induce innate immune responses.
authors.affiliation: Department of Dermatology, the University of Texas Southwestern Medical Center and Dermatology Section (Medical Service), Dallas Veterans Affairs Medical Center, Dallas, TX 75390, USA.
authors.forename: Kota
authors.initials: K
authors.lastname: Sato
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Yang
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yudate
authors.forename: Jin-Sung
authors.initials: JS
authors.lastname: Chung
authors.forename: Jianming
authors.initials: J
authors.lastname: Wu
authors.forename: Kate
authors.initials: K
authors.lastname: Luby-Phelps
authors.forename: Robert P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: David
authors.initials: D
authors.lastname: Underhill
authors.forename: Ponciano D
authors.initials: PD
authors.lastname: Cruz
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ariizumi
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D005658:Fungi / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D047468:Immunoprecipitation; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011961:Receptors, Fc / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D017931:DNA Primers; D053590:Interleukin 1 Receptor Antagonist Protein; D037181:Lectins, C-Type; D016328:NF-kappa B; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; C445340:dectin-2, mouse; D002118:Calcium