STAT4 is critical for immunity but not for antileishmanial activity of antimonials in experimental visceral leishmaniasis

Abstract

We and others have previously shown that IL-12 is indispensable for immunity and is required for the optimal antiparasitic activity of antimonials in experimental visceral leishmaniasis caused by Leishmania donovani. Here we investigated the role of STAT4 in immunity against L. donovani using STAT4 knockout mice and also determined the effect of STAT4 deficiency in response to antimonial therapy. Upon infection with L. donovani, stat4⁻/⁻ BALB/c and C57BL/6 mice showed enhanced susceptibility to Leishmania during late time points of infection which was associated with a marked reduction in Th1 responses and hepatic immunopathology. Interestingly, these defects in Th1 responses in stat4⁻/⁻ did not impair the antimonial chemotherapy as both stat4⁻/⁻ and WT mice showed comparable levels of parasite clearance from the liver and spleen. These findings highlight the role of STAT4 in immunity to L. donovani infection and also provide evidence that STAT4 is dispensable for antimonial-based chemotherapy.

Keywords: IFN-γ; IL-12; Leishmania donovani; STAT4 chemotherapy; Sodium stibogluconate.