Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity

Dominikus Strasser, Konstantin Neumann, Hanna Bergmann, Mohlopheni J. Marakalala, Reto Guler, Anna Rojowska, Karl-Peter Hopfner, Frank Brombacher, Henning Urlaub, Gottfried Baier, Gordon D. Brown, Michael Leitges, Jürgen Ruland

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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-delta (PKCdelta) was activated upon Dectin-1-Syk signaling, mediated phosphorylation of Card9 at Thr231, and was responsible for Card9-Bcl10 complex assembly and canonical NF-kappaB control. Prkcd(-/-) dendritic cells, but not those lacking PKCalpha, PKCß, or PKCtheta, 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, PKCd is an essential link between Syk activation and Card9 signaling for CLR-mediated innate immunity and host protection.
Original languageEnglish
Pages (from-to)32-42
Number of pages11
JournalImmunity
Volume36
Issue number1
Early online date19 Jan 2012
DOIs
Publication statusPublished - 27 Jan 2012

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Strasser, D., Neumann, K., Bergmann, H., Marakalala, M. J., Guler, R., Rojowska, A., ... Ruland, J. (2012). Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity. Immunity, 36(1), 32-42. https://doi.org/10.1016/j.immuni.2011.11.015