Susceptibility to Leishmania mexicana infection is due to the inability toproduce IL-12 rather than lack of IL-12 responsiveness

Almost all inbred mice are highly susceptible to parasites of the Leishmani a mexicana complex that includes L. amazonensis and L. mexicana. Recent stu dies have reported that T cells from L. amazonensis-infected mice fail to r espond to IL-12 due to impaired IL-12R expression. Here, we demonstrate tha t lymph node cells from L. mexicana-infected C57BL/6 and 129Sv/Ev mice resp ond efficiently to exogenous IL-12 in vitro and produce IFN-gamma. Moreover , we also show that deletion of signal transducer and activator of transcri ption (STAT)4 gene in resistant STAT6(-/-) mice renders them susceptible to L. mexicana. These findings indicate that an inability to produce IL-12 ra ther than unresponsiveness to this cytokine is responsible for susceptibili ty to L. mexicana. Moreover, the data also demonstrate that the STAT4-media ted pathway is critical for the development of protective immunity against cutaneous leishmaniasis, regardless of the species of Leishmania and/or gen etic background of the mice.