Immunization with heat-killed Toxoplasma gondii stimulates an early IFN-γ response and induces protection against virulent murine malaria

Abstract

In this study, we describe protection of BALB/c mice by immunization with heat-killed T. gondii tachyzoites against infection with Plasmodium yoelii 17XL which causes cerebral malaria and death in mice by day 7–8 post infection. Immunization resulted significant reduction in parasitemia at the peak period of infection. Protection induced by heat-killed T. gondii was associated with marked increase in NK cell number and IFN-γ mRNA expression early in the infection. The level of IFN-γ or TNF-α was found to diminish in T. gondii-treated mice as the infection progressed to the late stage. This declined response of IFN-γ or TNF-α was associated with marked increase in the expression of IL-10, a counterregulatory cytokine. Pretreatment of mice with live T. gondii induced poor level of protection as compared with that of heat-killed parasites. Mice that received P. yoelii infection alone, had an elevated IFN-γ response in the late stage of infection. Development of cerebral malaria in untreated mice was accompanied by an augmented production of TNF-α and nitric oxide (NO), the proinflammatory mediators. These findings suggest that nonspecific immunization with T. gondii leads to restoration of an early IFN-γ response in P. yoelii-infected mice and in the establishment of an immunoregulatory mechanism that effectively antagonizes the disease-promoting effects of proinflammatory cytokines in the late phase of infection.