| First Author | Settles EW | Year | 2014 |
| Journal | Infect Immun | Volume | 82 |
| Issue | 3 | Pages | 1343-53 |
| PubMed ID | 24396042 | Mgi Jnum | J:209405 |
| Mgi Id | MGI:5567064 | Doi | 10.1128/IAI.01259-13 |
| Citation | Settles EW, et al. (2014) Toxoplasma gondii upregulates interleukin-12 to prevent Plasmodium berghei-induced experimental cerebral malaria. Infect Immun 82(3):1343-53 |
| abstractText | 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-gamma). By 5 days after P. berghei infection, STAg-treated mice had reduced IFN-gamma levels compared to those of mock-treated mice, suggesting that reductions in IFN-gamma at the time of ECM onset protected against lethality. Using IL-10- and IL-12betaR-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-gamma and reduction in parasitemia. These results highlight the importance of early IL-12 induction in protection against ECM. |
