IL-12 gene-deficient C57BL/6 mice are susceptible to Leishmania donovani but have diminished hepatic immunopathology

To determine the in vivo role of IL-12 in the development of protective immunity in visceral leishmaniasis caused by Leishmania donovani, we examined the course of L. donovani infection in IL-12-deficient C57BL/6 (IL-12(-/-)) mice. IL-12-/- mice displayed significantly higher parasite burdens in their livers and spleens than wild-type C57BL/6 mice throughout the course of infection. Despite high parasite burdens, the onset of hepatosplenomegaly was significantly delayed in L. donovani-infected IL-12(-/-). Moreover, livers and spleens from IL-12(-/-) mice displayed significantly less inflammation and poorly formed granulomatous lesions than those from IL-12(-/-) mice throughout the course of infection. Antigen-stimulated splenocytes from IL-12(-/-) mice produced significantly less IFN-γ but more IL-4 than IL-12(-/-) mice. These findings indicate that although endogenous IL-12 is critical for the development of protective immunity to L. donovani, it is also responsible for inducing the significant immunopathology associated with visceral leishmaniasis.