Endogenous IL-13 Plays a Crucial Role in Liver Granuloma Maturation During Leishmania donovani Infection, Independent of

Previous studies comparing interleukin 4 receptor a (IL-4Ra)-/- and interleukin 4 (IL-4)-/- BALB/c mice have indicated that interleukin 13 (IL-13), whose receptor shares the IL-4Ra subunit with IL-4, plays a protective role during visceral leishmaniasis. We demonstrate that IL-13-/- BALB/c mice were less able to control hepatic growth of Leishmania donovani compared with wild-type mice. This correlated with significantly retarded granuloma maturation in IL-13-/- mice, defective interferon c (IFN-c) production, and elevated IL-4 and interleukin 10 (IL-10) levels. L. donovani–infected IL-13-/- mice also responded poorly to sodium stibogluconate-mediated chemotherapy compared with wild-type BALB/c mice. Because murine lymphocytes do not have IL-13 receptors, we examined the ability of macrophage/neutrophil-specific IL-4Ra-/- mice to control primary infection with L. donovani and to respond to chemotherapy. Macrophage/neutrophil-specific IL-4Ra-/- mice were as resistant to leishmaniasis as wild-type mice, and chemotherapy retained its efficacy. Consequently, in L. donovani infected BALB/c mice, IL-13 promotes hepatic granuloma formation and controls parasite burdens independently of direct effects on macrophages/neutrophils. Infection with the intracellular protozoan parasite Leishmania donovani causes a potentially fatal disease wherein macrophages of the viscera including the spleen