Susceptibility to <i>Leishmania mexicana</i> infection is due to the inability to produce IL‐12 rather than lack of IL‐12 responsiveness

Abstract

Almost all inbred mice are highly susceptible to parasites of the Leishmania mexicana complex that includes L. amazonensis and L. mexicana. Recent studies have reported that T cells from L. amazonensis-infected mice fail to respond to IL-12 due to impaired IL-12R expression. Here, we demonstrate that lymph node cells from L. mexicana-infected C57BL/6 and 129Sv/Ev mice respond efficiently to exogenous IL-12 in vitro and produce IFN-gamma. Moreover, we also show that deletion of signal transducer and activator of transcription (STAT)4 gene in resistant STAT6-/- mice renders them susceptible to L. mexicana. These findings indicate that an inability to produce IL-12 rather than unresponsiveness to this cytokine is responsible for susceptibility to L. mexicana. Moreover, the data also demonstrate that the STAT4-mediated pathway is critical for the development of protective immunity against cutaneous leishmaniasis, regardless of the species of Leishmania and/or genetic background of the mice.