IL-13 gene-deficient mice are susceptible to cutaneous L-mexicana infection

Recent studies have demonstrated that IL-13 mediates susceptibility to cuta neous L. major infection via I L-4-independent pathway. To determine whethe r IL-13 also plays a similar role in pathogenesis of cutaneous L. mexicana infection, we analyzed the course of L. mexicana infection in IL-13(-/-) an d IL-4/IL-13(-/-) C57BL/6x129sv/Ev mice and compared with that in similarly infected wild-type mice. IL-13(-/-) mice were as susceptible as the wild-t ype mice to L. mexicana and developed rapidly progressing, large non-healin g lesions following cutaneous L. mexicana infection. In contrast, similarly infected IL-4/IL-13(-/-) mice were highly resistant and developed either n o lesions or small lesions containing few parasites that totally resolved b y 12 weeks following infection. Throughout the course of infection IL-13(-/ -) and the wild-type mice produced significantly more Th2-associated L. mex icana antigen (LmAg)-specific IgG1 than IL-4/IL-13(-/-) mice. All three gro ups produced comparable levels of Th1-associated IgG2a. At week 12 post inf ection, LmAg-stimulated spleen cells from L. mexicana-infected IL-4/IL-13(- /-) produced significantly higher levels of IL-12 and IFN-gamma as compared to those from similarly infected wild-type and IL-13(-/-) mice. Although b oth IL-13(-/-) and the wild-type spleen cells produced IL-4 following in vi tro antigenic stimulation, the wildtype mice produced significantly more. T hese findings demonstrate that IL-13 is not involved in mediating susceptib ility to L. mexicana. Moreover, they also indicate that IL-4 not IL-13 is a dominant cytokine involved in pathogenesis of cutaneous L. mexicana infect ion.