Infect Immun. 2014 Jan 6. [Epub ahead of print]
Toxoplasma gondii upregulates interleukin-12 to prevent Plasmodium berghei-induced experimental cerebral malaria
A pre-existing chronic infection with the parasite Toxoplasma gondii has previously been shown to protect mice against subsequent viral, bacterial or protozoal infections. Here we show 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 hours post P. berghei infection led to a rapid increase in serum levels of interleukin (IL)-12 and interferon-γ (IFN-γ). By five days after P. berghei infection, STAg treated mice had reduced IFN-γ levels compared to 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.
- [PubMed - as supplied by publisher]