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Fungal pattern receptors down‐regulate the inflammatory response by a cross‐inhibitory mechanism independent of interleukin‐10 production
Author(s) -
Rodríguez Mario,
Márquez Saioa,
Rosa Juan Vladimir,
Alonso Sara,
Castrillo Antonio,
Sánchez Crespo Mariano,
Fernández Nieves
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12678
Subject(s) - zymosan , microbiology and biotechnology , cytokine , stat protein , biology , signal transduction , tyrosine phosphorylation , stat3 , immunology , chemistry , biochemistry , in vitro
Summary Cyclic AMP regulatory element binding protein and signal transducer and activator of transcription 3 ( STAT 3) may control inflammation by several mechanisms, one of the best characterized is the induction of the expression of the anti‐inflammatory cytokine interleukin‐10 ( IL ‐10). STAT 3 also down‐regulates the production of pro‐inflammatory cytokines induced by immunoreceptor tyrosine‐based activation motif ( ITAM )‐coupled receptors, a mechanism termed cross‐inhibition. Because signalling via ITAM ‐dependent mechanisms is a hallmark of fungal pattern receptors, STAT 3 activation might be involved in the cross‐inhibition associated with invasive fungal infections. The fungal surrogate zymosan produced the phosphorylation of Y705‐ STAT 3 and the expression of Ifnb1 and Socs3 , but did not induce the interferon ( IFN )‐signature cytokines Cxcl9 and Cxcl10 in bone marrow‐derived dendritic cells. Unlike lipopolysaccharide ( LPS ), zymosan induced IL ‐10 and phosphorylated Y705‐ STAT 3 to a similar extent in Irf3 and Ifnar1 knockout and wild‐type mice. Human dendritic cells showed similar results, although the induction of IFNB 1 was less prominent. These results indicate that LPS and zymosan activate STAT 3 through different routes. Whereas type I IFN is the main effector of LPS effect, the mechanism involved in Y705‐ STAT 3 phosphorylation by zymosan is more complex, cannot be associated with type I IFN , IL ‐6 or granulocyte–macrophage colony‐stimulating factor, and seems dependent on several factors given that it was partially inhibited by the platelet‐activating factor antagonist WEB 2086 and high concentrations of COX inhibitors, p38 mitogen‐activate protein kinase inhibitors, and blockade of tumour necrosis factor‐ α function. Altogether, these results indicate that fungal pattern receptors share with other ITAM ‐coupled receptors the capacity to produce cross‐inhibition through a mechanism involving STAT 3 and induction of SOCS 3 and IL ‐10, but that cannot be explained through type I IFN signalling.