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Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors

Dennehy, Kevin M., Ferwerda, Gerben, Faro-Trindade, Inês, Pyz, Elwira, Willment, Janet A., Taylor, Philip Russel ORCID:, Kerrigan, Ann, Tsoni, S. Vicky, Gordon, Siamon, Meyer-Wentrup, Friederike, Adema, Gosse J., Kullberg, Bart-Jan, Schweighoffer, Edina, Tybulewicz, Victor, Mora-Montes, Hector M., Gow, Neil A. R., Williams, David L., Netea, Mihai G. and Brown, Gordon D. 2008. Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors. European Journal of Immunology 38 (2) , pp. 500-506. 10.1002/eji.200737741

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Recognition of microbial components by germ-line encoded pattern recognition receptors (PRR) initiates immune responses to infectious agents. We and others have proposed that pairs or sets of PRR mediate host immunity. One such pair comprises the fungal β-glucan receptor, Dectin-1, which collaborates through an undefined mechanism with Toll-like receptor 2 (TLR2) to induce optimal cytokine responses in macrophages. We show here that Dectin-1 signaling through the spleen tyrosine kinase (Syk) pathway is required for this collaboration, which can also occur with TLR4, 5, 7 and 9. Deficiency of either Syk or the TLR adaptor MyD88 abolished collaborative responses, which include TNF, MIP-1 and MIP-2 production, and which are comparable to the previously described synergy between TLR2 and TLR4. Collaboration of the Syk and TLR/MyD88 pathways results in sustained degradation of the inhibitor of kB (IkB), enhancing NFkB nuclear translocation. These findings establish the first example of Syk- and MyD88-coupled PRR collaboration, further supporting the concept that paired receptors collaborate to control infectious agents.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: C-type lectin ; Innate immunity ; Macrophage ; Syk ; TLR
Publisher: John Wiley & Sons
ISSN: 0014-2980
Last Modified: 19 Oct 2022 09:52

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