title: Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity.
abstract: C-type lectin receptors (CLRs) that couple with the kinase Syk are major pattern recognition receptors for the activation of innate immunity and host defense. CLRs recognize fungi and other forms of microbial or sterile danger, and they induce inflammatory responses through the adaptor protein Card9. The mechanisms relaying CLR proximal signals to the core Card9 module are unknown. Here we demonstrated that protein kinase C-δ (PKCδ) was activated upon Dectin-1-Syk signaling, mediated phosphorylation of Card9 at Thr231, and was responsible for Card9-Bcl10 complex assembly and canonical NF-κB control. Prkcd(-/-) dendritic cells, but not those lacking PKCα, PKCβ, or PKCθ, were defective in innate responses to Dectin-1, Dectin-2, or Mincle stimulation. Moreover, Candida albicans-induced cytokine production was blocked in Prkcd(-/-) cells, and Prkcd(-/-) mice were highly susceptible to fungal infection. Thus, PKCδ is an essential link between Syk activation and Card9 signaling for CLR-mediated innate immunity and host protection.
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Dominikus
authors.initials: D
authors.lastname: Strasser
authors.forename: Konstantin
authors.initials: K
authors.lastname: Neumann
authors.forename: Hanna
authors.initials: H
authors.lastname: Bergmann
authors.forename: Mohlopheni J
authors.initials: MJ
authors.lastname: Marakalala
authors.forename: Reto
authors.initials: R
authors.lastname: Guler
authors.forename: Anna
authors.initials: A
authors.lastname: Rojowska
authors.forename: Karl-Peter
authors.initials: KP
authors.lastname: Hopfner
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Gottfried
authors.initials: G
authors.lastname: Baier
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Jürgen
authors.initials: J
authors.lastname: Ruland
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D002176:Candida albicans / Q000276:immunology; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology*; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta