Simplexide induces CD1d-dependent cytokine and chemokine production from human monocytes

Abstract

Monocytes are major effector cells of innate immunity and recognize several endogenous and exogenous molecules due to the expression of wide spectrum of receptors. Among them, the MHC class I-like molecule CD1d interacts with glycolipids and presents them to iNKT cells, mediating their activation. Simplexide belongs to a novel class of glycolipids isolated from marine sponges and is structurally distinct from other immunologically active glycolipids. In this study we have examined the effects of simplexide on cytokine and chemokine release from human monocytes. Simplexide induces a concentrationand time-dependent release of IL-6, CXCL8, TNF-a and IL-10 and increases the expression of IL6, CXCL8 and IL10 mRNA. Cytokine and chemokine release induced by simplexide from monocytes is dependent on CD1d since: i) a CD1d antagonist, 1,2-bis (diphenylphosphino) ethane [DPPE]- polyethylene glycolmonomethylether [PEG], specifically blocks simplexideinduced activation of monocytes; ii) CD1d knockdown inhibits monocyte activation by simplexide and iii) simplexide induces cytokine production from CD1d-transfected but not parental C1R cell line Finally, we have shown that simplexide also induces iNKT cell expansion in vitro. Our results demonstrate that simplexide, apart from activating iNKT cells, induces the production of cytokines and chemokines from human monocytes by direct interaction with CD1d. This Funding: This work was supported by grants from the Ministero dell Universita e della Ricerca (MT, and GM), the Regione Campania (GM), CISI Lab project, CRE ME project, TIMING project and European Union s Seventh Framework Programme FP7/2007-2013 under grant agreement nu 311848 (BlueGenics) (AM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.