TLR adaptor MyD88 is essential for pathogen control during oral toxoplasma gondii infection but not adaptive immunity induced by a vaccine strain of the parasite.
TLR adaptor MyD88 activation is important in host resistance to Toxoplasma gondii during i.p. infection, but the function of this signaling pathway during oral infection, in which mucosal immunity assumes a predominant role, has not been examined. In this study, we show that MyD88(-/-) mice fail to control the parasite and succumb within 2 wk of oral infection. Early during infection, T cell IFN-gamma production, recruitment of neutrophils and induction of p47 GTPase IGTP (Irgm3) in the intestinal mucosa were dependent upon functional MyD88. Unexpectedly, these responses were MyD88-independent later during acute infection. In particular, CD4(+) T cell IFN-gamma reached normal levels independently of MyD88, despite continued absence of IL-12 in these animals. The i.p. vaccination of MyD88(-/-) mice with an avirulent T. gondii uracil auxotroph elicited robust IFN-gamma responses and protective immunity to challenge with a high virulence T. gondii strain. Our results demonstrate that MyD88 is required to control Toxoplasma infection, but that the parasite can trigger adaptive immunity without the need for this TLR adaptor molecule.
Sukhumavasi
Woraporn
W
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Egan
Charlotte E
CE
Warren
Amy L
AL
Taylor
Gregory A
GA
Fox
Barbara A
BA
Bzik
David J
DJ
Denkers
Eric Y
EY
D000818:Animals; D005260:Female; D007109:Immunity; D007371:Interferon-gamma / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology*; D016052:Protozoan Vaccines / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000276:immunology*
D053594:Myeloid Differentiation Factor 88; D016052:Protozoan Vaccines; D007371:Interferon-gamma