Susceptibility to Leishmania major infection in the absence of IL-4.

Infection with the intracellular parasite Leishmania major is the prototypical model system used to study Th1 and Th2 cytokine responses in vivo. Mouse strains that are resistant to L. major produce high levels of IFNgamma, and Th1 cytokines while susceptible BALB/c mice have elevated levels of IL-4, and Th2-associated cytokines during infection. While antibody neutralization of IL-4 or IFNgamma in vivo alters the disease patterns, infection of mice genetically deficient for IL-4 or IL-4 receptor (IL-4Ralpha) yield surprising outcomes. Contrary to the Th1/Th2 paradigm, IL-4- / - and IL-4Ralpha -/ - mice remain highly susceptible to L. major parasite substrain LV39. In distinct contrast, another L. major substrain. IR173, the IL-4Ralpha - / -mice are highly resistant. These findings indicate a disparity between antibody treatment versus gene deletion, and more generally, challenge the role of IL-4 in promoting susceptibility to L. major. Furthermore, IL-4Ralpha - / - mice reveal that the ability of L. major to escape immune clearance depends on the parasite substrain.