MyD88 is required for resistance to toxoplasma gondii infection and fregulates parasite-induced IL-12 production by dendritic cells

摘要

Host resistance to the intracellular protozoan toxoplasma gondii is highly dependent on early IL-12 production by APC.We demonstrate here that both host resistance and T.gondii-in-duced IL-12 production are dramatically reduced in mice lacking the adaptor molecule MyD88,an important signaling element used by Toll-like receptor (TLR) family members.Infection of MyD88-dificient mice with T.gondii resulted in uncontrolled parasite replication nd greatly reduced plasma IL-12 levels.Defective IL-12 responses to T.gondii Ags (soluble tachyzoite Ag(STAg)) were observed in MyD88~(-/-) peritoneal macrophages,neutrophils,and splenic dendritic cells (DC).In contrast,DC from TLR2- or TLR4-deficient animals developed normal IL-12 responses to STAg.In vivo treatment with pertussis toxin abolished the residual IL-12 response displayed by STAg-stimulated DC from MyD88~(-/-) mice.Taken together,these data suggest that the induction of IL-12 by T.gondii depends on a unique mechanism involving both MyD88 and G protein-coupled signaling pathways.