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* Institute for Infectious Diseases and Molecular Medicine and Division of Immunology, Health Science Faculty, University of Cape Town, Cape Town, South Africa; and
Junior Research Group Molecular Infection Biology, Research Center, Borstel, Germany
Expressed on various cell types, the IL-4R
is a component of both receptors for IL-4 and IL-13. Susceptibility of BALB/c mice to Leishmania major is believed to be dependent on the development of IL-4- and IL-13-producing Th2 cells, while IFN-
secretion by Th1 cells is related to resistance. Despite a sustained development of Th2 cells, IL-4R-deficient BALB/c mice are able to control acute cutaneous leishmaniasis, suggesting that IL-4R-bearing cells other than Th2 cells contribute to susceptibility. To analyze the contribution of the IL-4R on macrophages, recently generated macrophage/neutrophil-specific IL-4R-deficient mice on a susceptible BALB/c genetic background were infected with L. major. Strikingly, macrophage/neutrophil-specific IL-4R-deficient mice showed a significantly delayed disease progression with normal Th2 and type 2 Ab responses but improved macrophage leishmanicidal effector functions and reduced arginase activity. Together, these results suggest that alternative macrophage activation contributes to susceptibility in cutaneous leishmaniasis.
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