IL-4 mediated resistance of BALB/c mice to visceral leishmaniasis is independent of IL-4Rα signaling via T cells

McFarlane, Emma and Mokgethi, Thabang and Kaye, Paul M. and Hurdayal, Ramona and Brombacher, Frank and Alexander, James and Carter, Katharine C. (2019) IL-4 mediated resistance of BALB/c mice to visceral leishmaniasis is independent of IL-4Rα signaling via T cells. Frontiers in Immunology, 10. 1957. ISSN 1664-3224 (https://doi.org/10.3389/fimmu.2019.01957)

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Abstract

Previous studies infecting global IL-4Rα −/−, IL-4 −/−, and IL-13 −/− mice on a BALB/c background with the visceralizing parasite Leishmania donovani have shown that the T helper 2 cytokines, IL-4, and IL-13, play influential but not completely overlapping roles in controlling primary infection. Subsequently, using macrophage/neutrophil-specific IL-4Rα deficient BALB/c mice, we demonstrated that macrophage/neutrophil unresponsiveness to IL-4 and IL-13 did not have a detrimental effect during L. donovani infection. Here we expand on these findings and show that CD4 + T cell-(Lck cre), as well as pan T cell-(iLck cre) specific IL-4Rα deficient mice, on a BALB/c background, unlike global IL-4Rα deficient mice, are also not adversely affected in terms of resistance to primary infection with L. donovani. Our analysis suggested only a transient and tissue specific impact on disease course due to lack of IL-4Rα on T cells, limited to a reduced hepatic parasite burden at day 30 post-infection. Consequently, the protective role(s) demonstrated for IL-4 and IL-13 during L. donovani infection are mediated by IL-4Rα-responsive cell(s) other than macrophages, neutrophils and T cells.