IL-13 is a susceptibility factor for Leishmania major infection

Leishmania major infection is useful as an experimental model to define fac tors responsible for the development and maintenance of Th cell immune resp onses. Studies using inbred mouse strains have identified that the Till res ponse characteristic of C57BL/6 mice results in healing, whereas BALB/c mic e fail to control the infection due to the generation of an inappropriate T h2 response. We now demonstrate that IL-13 is a key factor in determining s usceptibility to L, major infection, Overexpression of IL-13 in transgenic mice makes the normally resistant C57BL/6 mouse strain susceptible to L. ma jor infection even in the absence of IL-4 expression. This susceptibility c orrelates with a suppression of 1L-12 and IFN-gamma expression. Furthermore , using BALB/c mice deficient in the expression of IL-4, IL-13, or both IL- 13 and IL-4, we demonstrate that IL-13-deficient mice are resistant to infe ction and that there is an additive effect of deleting both IL-4 and IL-13.