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Stage-Specific Expression of Surface Antigens by Toxoplasma gondii as a Mechanism to Facilitate Parasite Persistence¹

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305

Toxoplasma persists in the face of a functional immune system. This success critically depends on the ability of parasites to activate a strong adaptive immune response during acute infection with tachyzoites that eliminates most of the parasites and to undergo stage conversion to bradyzoites that encyst and persist predominantly in the brain. A dramatic change in antigenic composition occurs during stage conversion, such that tachyzoites and bradyzoites express closely related but antigenically distinct sets of surface Ags belonging to the surface Ag 1 (SAG1)-related sequence (SRS) family. To test the contribution of this antigenic switch to parasite persistence, we engineered parasites to constitutively express the normally bradyzoite-specific SRS9 (SRS9^c) mutants and tachyzoite-specific SAG1 (SAG1^c) mutants. SRS9^c but not wild-type parasites elicited a SRS9-specific immune response marked by IFN- production, suggesting that stage-specificity of SRS Ags determines their immunogenicity in infection. The induction of a SRS9-specific immune response correlated with a continual decrease in the number of SRS9^c cysts persisting in the brain. In contrast, SAG1^c mutants produced reduced brain cyst loads early in chronic infection, but these substantially increased over time accompanying a hyperproduction of IFN-, TNF-, and IL-10, and severe encephalitis. We conclude that stage-specific expression of SRS Ags is among the key mechanisms by which optimal parasite persistency is established and maintained.

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The JI 2005 174: 7477-7478. [Full Text]  

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