Cutting edge: MyD88 is required for resistance to Toxoplasma gondii infection and regulates parasite-induced IL-12 production by dendritic cells.

• 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.
• Authors: Charles A Scanga, Julio Aliberti, Dragana Jankovic, Florence Tilloy, Soumaya Bennouna, Eric Y Denkers, Ruslan Medzhitov, Alan Sher (Affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. cscanga at niaid.nih.gov)
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 168 Issue 12 Pg. 5997-6001 (Jun 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12055206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antigens, Differentiation
• Drosophila Proteins
• Membrane Glycoproteins
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• Receptors, CCR5
• Receptors, Cell Surface
• Receptors, Immunologic
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Toll-Like Receptors
• Interleukin-12
• Interferon-gamma

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Antigens, Differentiation (genetics, physiology)
• Dendritic Cells (immunology, metabolism, parasitology)
• Drosophila Proteins
• Female
• Immunity, Innate (genetics)
• Interferon-gamma (biosynthesis, deficiency)
• Interleukin-12 (biosynthesis, deficiency)
• Macrophages, Peritoneal (immunology, metabolism, parasitology)
• Male
• Membrane Glycoproteins (deficiency, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Differentiation Factor 88
• Neutrophils (immunology, metabolism, parasitology)
• Receptors, CCR5 (physiology)
• Receptors, Cell Surface (deficiency, physiology)
• Receptors, Immunologic (deficiency, genetics, physiology)
• Signal Transduction (immunology)
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Toll-Like Receptors
• Toxoplasma (immunology)
• Toxoplasmosis, Animal (genetics, immunology, mortality, parasitology)