Quantification of Leishmania major parasites in dendritic cells deficient for IL-4Rα signalling in BALB/c mice

Abstract

Susceptibility and resistance in cutaneous Leishmania major infection, is characterised by induction of distinct subsets of immunological response. BALB/c mice display susceptibility to L. major infection, developing T helper 2 (Th2) cell dominated responses with production of cytokines Interleukin-4 (IL-4) and IL-13. In contrast, resistant C57BL/6 mice catalyse Th1 dominated immune responses with increased IL-12 and Interferon-gamma (IFNγ). Th1 responses are associated with classical macrophage activation and parasite killing via inducible nitrous oxide synthase(iNOs). Paradoxically IL-4 administration during dendritic (DC) priming has been demonstrated to induce IL-12 production by these DC’s and instruct a Th1 dominant response. To elucidate the role of endogenous IL-4 levels on DC mediated T cell education, BALB/c mice deficient for the IL-4 receptor α chain (a receptor shared between IL-4 and IL-13) specifically on DCs were generated by gene rearrangement. These CD11c^creIL-4Rα^-/lox mice show hypersusceptibility to L. major infection with increased footpad swelling, peripheral parasite load and reduced iNOS in both macrophages and DCs. Confocal microscopy shows these DCs to be major etiological factors in disease dissemination due to their migratory capacity and reduced parasite killing functions in the absence of early IL-4Rα mediated response.