In experimental leishmaniasis deficiency of CD18 results in parasite dissemination associated with altered macrophage functions and incomplete Th1 cell response

We investigated experimental leishmaniasis in CD18‐deficient mice. Whereas wild‐type (WT) CD18+/+ mice (129SV/C57BL/6) were resistant to infection, CD18–/– mice revealed increasing visceral dissemination of parasites. Unlike in other susceptible strains, infected footpads of CD18–/– mice did not ulcerate, due to an abolished recruitment of granulocytes. In vitro, CD18–/– macrophages were able to phagocytose opsonized Leishmania major despite absence of CR3, albeit phagocytosis rate was 50% lower than in WT macrophages. We found that uptake was partially mediated by scavenger receptors. As infected CD18–/– macrophages showed impaired ability to produce NO and to eliminate parasites, CD18 is one mediator of NO production. CD18 is also involved in reduction of IL‐12 release by L. major‐infected macrophages, as uptake of opsonized parasites (via CR3) decreased IL‐12 release only in WT, but not in CD18–/– macrophages. When T cells from infected CD18–/– mice were restimulated with antigen‐presenting cells (APC), they released no IL‐2 or IL‐4, but a little IFN‐γ, associated with lack of proliferation. This deficiency was linked to absence of CD18 on T cells, but not on APC. Substitution with IL‐2 specifically restored a Th1‐like response with proliferation and release of IFN‐γ. Thus, while impaired phagocytosis, NO production, and recruitment of granulocytes in CD18–/– mice may not reverse resistance, and while unrestricted IL‐12 release supports development of Th1 cells, the failure to of T cells release IL‐2 and to proliferate causes susceptibility.