title: Phosphoinositide-3-kinase-dependent, MyD88-independent induction of CC-type chemokines characterizes the macrophage response to Toxoplasma gondii strains with high virulence.
abstract: Chemokines play an important role in inflammation and infection due to their ability to recruit cells of innate and adaptive immunity. Here we examined mouse macrophage chemokine responses during intracellular infections with high- and low-virulence Toxoplasma gondii strains. The high-virulence type I strain RH induced a large panel of CC-type chemokines, whereas responses elicited by strains PTG (type II) and M7741 (type III) were much weaker. Strikingly, the T. gondii-induced chemokine response occurred independently of signaling through the Toll-like receptor adaptor MyD88. Instead, production of chemokines during infection was heavily dependent upon phosphoinositide-3-kinase signaling pathways. Because infection with type I strains such as RH results in an uncontrolled proinflammatory cytokine response, we hypothesize that this virulence phenotype is a consequence of early strong induction of chemokines by type I, but not type II or III, Toxoplasma strains.
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401, USA.
authors.forename: Chiang W
authors.initials: CW
authors.lastname: Lee
authors.forename: Woraporn
authors.initials: W
authors.lastname: Sukhumavasi
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Denkers
mesh_terms: D000818:Animals; D054414:Chemokine CCL17 / Q000276:immunology; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014122:Toxoplasma / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D014774:Virulence
chemical_list: C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D019869:Phosphatidylinositol 3-Kinases