title: Toxoplasma gondii upregulates interleukin-12 to prevent Plasmodium berghei-induced experimental cerebral malaria.
abstract: A chronic infection with the parasite Toxoplasma gondii has previously been shown to protect mice against subsequent viral, bacterial, or protozoal infections. Here we have shown that a chronic T. gondii infection can prevent Plasmodium berghei ANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. Treatment with soluble T. gondii antigens (STAg) reduced parasite sequestration and T cell infiltration in the brains of P. berghei-infected mice. Administration of STAg also preserved blood-brain barrier function, reduced ECM symptoms, and significantly decreased mortality. STAg treatment 24 h post-P. berghei infection led to a rapid increase in serum levels of interleukin 12 (IL-12) and gamma interferon (IFN-γ). By 5 days after P. berghei infection, STAg-treated mice had reduced IFN-γ levels compared to those of mock-treated mice, suggesting that reductions in IFN-γ at the time of ECM onset protected against lethality. Using IL-10- and IL-12βR-deficient mice, we found that STAg-induced protection from ECM is IL-10 independent but IL-12 dependent. Treatment of P. berghei-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-γ and reduction in parasitemia. These results highlight the importance of early IL-12 induction in protection against ECM.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin, USA.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Settles
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Moser
authors.forename: Tajie H
authors.initials: TH
authors.lastname: Harris
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Knoll
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000382:microbiology; D001921:Brain / Q000276:immunology / Q000382:microbiology; D016466:CHO Cells; D003412:Cricetulus; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D016779:Malaria, Cerebral / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000276:immunology / Q000382:microbiology; D010962:Plasmodium berghei / Q000276:immunology*; D053702:Receptors, Interleukin-11 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology / Q000382:microbiology; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D053702:Receptors, Interleukin-11; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma