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Here we have shown that a chronic<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>infection can prevent<jats:named-content content-type=\"genus-species\">Plasmodium berghei<\/jats:named-content>ANKA-induced experimental cerebral malaria (ECM) in C57BL\/6 mice. Treatment with soluble<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>antigens (STAg) reduced parasite sequestration and T cell infiltration in the brains of<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>-infected mice. Administration of STAg also preserved blood-brain barrier function, reduced ECM symptoms, and significantly decreased mortality. STAg treatment 24 h post-<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>infection led to a rapid increase in serum levels of interleukin 12 (IL-12) and gamma interferon (IFN-\u03b3). By 5 days after<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>infection, STAg-treated mice had reduced IFN-\u03b3 levels compared to those of mock-treated mice, suggesting that reductions in IFN-\u03b3 at the time of ECM onset protected against lethality. Using IL-10- and IL-12\u03b2R-deficient mice, we found that STAg-induced protection from ECM is IL-10 independent but IL-12 dependent. Treatment of<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>-infected mice with recombinant IL-12 significantly decreased parasitemia and mortality. These data suggest that IL-12, either induced by STAg or injected as a recombinant protein, mediates protection from ECM-associated pathology potentially through early induction of IFN-\u03b3 and reduction in parasitemia. These results highlight the importance of early IL-12 induction in protection against ECM.<\/jats:p>","DOI":"10.1128\/iai.01259-13","type":"journal-article","created":{"date-parts":[[2014,1,7]],"date-time":"2014-01-07T04:37:56Z","timestamp":1389069476000},"page":"1343-1353","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Toxoplasma gondii Upregulates Interleukin-12 To Prevent Plasmodium berghei-Induced Experimental Cerebral Malaria"],"prefix":"10.1128","volume":"82","author":[{"given":"Erik W.","family":"Settles","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey A.","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tajie H.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Knoll","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"S1","article-title":"Severe falciparum malaria","volume":"94","year":"2000","unstructured":". 2000. 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