title: CD36 modulates proinflammatory cytokine responses to Plasmodium falciparum glycosylphosphatidylinositols and merozoites by dendritic cells.
abstract: Studies have shown that glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum activate macrophages mainly through Toll-like receptor 2 (TLR2)-mediated signalling and to certain extent through TLR4-mediated signalling to induce proinflammatory cytokine production. However, the ability of parasite GPIs to activate dendritic cells (DCs) has not been reported. Here, we show that parasite GPIs efficiently activate DCs through TLR2-mediated signalling mechanism and induce the production of TNF-α and IL-12. We also studied the role of scavenger receptor CD36 in P. falciparum GPI- and merozoite-induced cytokine responses by DCs. The results indicate that CD36 modulates the cytokine-inducing activity of the parasite GPIs by collaborating with TLR2 in DCs. Furthermore, our data reveal that CD36 modulates the activity of P. falciparum merozoites, likely by the contribution of phagocytosis-coupled CD36-mediated signalling to the signalling induced by merozoites. Altogether, these results contribute towards understanding of signalling mechanisms in malaria parasite-induced activation of the innate immune system.
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: N M
authors.initials: NM
authors.lastname: Gowda
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: R N
authors.initials: RN
authors.lastname: Gowda
authors.forename: D C
authors.initials: DC
authors.lastname: Gowda
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D017261:Glycosylphosphatidylinositols / Q000276:immunology*; D052940:Merozoites / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010963:Plasmodium falciparum / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D016207:Cytokines; D017261:Glycosylphosphatidylinositols; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2