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

doi:10.1016/j.immuni.2011.11.015

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

Research output: Contribution to journal › Article › peer-review

206 Citations (Scopus)

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 language	English
Pages (from-to)	32-42
Number of pages	11
Journal	Immunity
Volume	36
Issue number	1
Early online date	19 Jan 2012
DOIs	https://doi.org/10.1016/j.immuni.2011.11.015
Publication status	Published - 27 Jan 2012

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10.1016/j.immuni.2011.11.015

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Strasser, D., Neumann, K., Bergmann, H., Marakalala, M. J., Guler, R., Rojowska, A., Hopfner, K-P., Brombacher, F., Urlaub, H., Baier, G., Brown, G. D., Leitges, M., & 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

Strasser, D, Neumann, K, Bergmann, H, Marakalala, MJ, Guler, R, Rojowska, A, Hopfner, K-P, Brombacher, F, Urlaub, H, Baier, G, Brown, GD, Leitges, M & Ruland, J 2012, 'Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity', Immunity, vol. 36, no. 1, pp. 32-42. https://doi.org/10.1016/j.immuni.2011.11.015

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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-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, PKC{\ss}, 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.",

author = "Dominikus Strasser and Konstantin Neumann and Hanna Bergmann and Marakalala, {Mohlopheni J.} and Reto Guler and Anna Rojowska and Karl-Peter Hopfner and Frank Brombacher and Henning Urlaub and Gottfried Baier and Brown, {Gordon D.} and Michael Leitges and J{\"u}rgen Ruland",

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doi = "10.1016/j.immuni.2011.11.015",

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T1 - Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity

AU - Strasser, Dominikus

AU - Neumann, Konstantin

AU - Bergmann, Hanna

AU - Marakalala, Mohlopheni J.

AU - Guler, Reto

AU - Rojowska, Anna

AU - Hopfner, Karl-Peter

AU - Brombacher, Frank

AU - Urlaub, Henning

AU - Baier, Gottfried

AU - Brown, Gordon D.

AU - Leitges, Michael

AU - Ruland, Jürgen

PY - 2012/1/27

Y1 - 2012/1/27

N2 - 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.

AB - 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.

U2 - 10.1016/j.immuni.2011.11.015

DO - 10.1016/j.immuni.2011.11.015

M3 - Article

C2 - 22265677

VL - 36

SP - 32

EP - 42

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 1

ER -

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

Abstract

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