Infect Immun. 2007 Jan 29; [Epub ahead of print]
Bradyzoite-specific surface antigen SRS9 plays a role in maintaining Toxoplasma persistence in the brain and in host control of parasite replication in the intestine
Kim SK, Karasov A, Boothroyd JC.
Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305.
Toxoplasma gondii is an ubiquitous parasite that persists for the life of a healthy mammalian host. A latent, chronic infection can reactivate upon immunosuppression and cause life-threatening diseases, such as encephalitis. A key to the pathogenesis is the parasite's interconversion between the tachyzoite (in acute infection) and bradyzoite (in chronic infection) stages. This developmental switch is marked by differential expression of numerous, closely related surface proteins belonging to the SRS (SAG1-related sequence) superfamily. To probe the functions of bradyzoite-specific SRSs, we created a bioluminescent strain lacking the expression of SRS9, one of the most abundant SRSs of the bradyzoite stage. Imaging of mice intraperitoneally infected with tachyzoites revealed that during an acute infection, wild type and Deltasrs9 strains replicated at similar rates, disseminated systemically following similar kinetics, and initially yielded similar brain cyst numbers. However, during a chronic infection, Deltasrs9 cyst loads substantially decreased compared to the wild type, suggesting that SRS9 plays a role in maintaining parasite persistence in the brain. In oral infection with bradyzoite cysts, the Deltasrs9 strain showed oral infectivity and dissemination patterns indistinguishable from the wild type. When chronically infected mice were treated with an immunosuppressant dexamethasone, however, the Deltasrs9 strain reactivated in the intestinal tissue after only 8-9 days, vs. 2 weeks for the wild type strain. Thus, SRS9 appears to play an important role in both persistence in the brain and reactivation in the intestine. Possible mechanisms for this are discussed.
PMID: 17261600 [PubMed - as supplied by publisher]