Cutting Edge: MyD88 Is Required for Resistance toToxoplasma gondiiInfection and Regulates Parasite-Induced IL-12 Production by Dendritic Cells
Top Cited Papers
- 15 June 2002
- journal article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 168 (12) , 5997-6001
- https://doi.org/10.4049/jimmunol.168.12.5997
Abstract
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-induced 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-deficient mice with T. gondii resulted in uncontrolled parasite replication and 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.Keywords
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