Altered immune response of interferon regulatory factor 1-deficient mice against Plasmodium berghei blood-stage malaria infection

Nitric oxide (NO) is a short-lived biological mediator which can be induced in various cell types and is able to cause many metabolic changes in targe t cells. Inhibition of tumor cell growth and antimicrobial activity has bee n attributed to the stimulation of NO production by transcriptional upregul ation of inducible nitric oxide synthase. In the present study, we used mic e devoid of functional interferon regulatory factor 1 by targeted gene disr uption (IRF-1(-/-)) to investigate the role of NO in the host immune respon se against blood-stage Plasmodium berghei ANKA infection. IRF-1(-/-) mice s urvived longer with a later onset of and a lower peak parasitemia despite t he inability to produce appreciable levels of NO. The administration of exo genous interleukin-12 (IL-12) was able to prolong survival in the wild-type mice with an upregulation in the expression of both gamma interferon (IFN- gamma) and NO. However, the administration of IL-12 did not improve the sur vival of IRF-1(-/-) mice. These studies indicate that while IL-12 is able t o mediate protection via an IFN-gamma- and NO-dependent pathway in the wild -type mice, such a protective mechanism may not be functional in the IRF-1( -/-) mice. Our results suggest that NO may not be essential for host immuni ty to the parasite and that IRF-1(-/-) mice are able to induce an IFN-gamma - and NO-independent mechanism against P. berghei infection.