Cross‐presenting dendritic cells are required for control of Leishmania major infection

Leishmania major infection induces self‐healing cutaneous lesions in C57BL/6 mice. Both IL‐12 and IFN‐γ are essential for the control of infection. We infected Jun dimerization protein p21SNFT (Batf3−/−) mice (C57BL/6 background) that lack the major IL‐12 producing and cross‐presenting CD8α+ and CD103+ DC subsets. Batf3−/− mice displayed enhanced susceptibility with larger lesions and higher parasite burden. Additionally, cells from draining lymph nodes of infected Batf3−/− mice secreted less IFN‐γ, but more Th2‐ and Th17‐type cytokines, mirrored by increased serum IgE and Leishmania‐specific immunoglobulin 1 (Th2 indicating). Importantly, CD8α+ DCs isolated from lymph nodes of L. major‐infected mice induced significantly more IFN‐γ secretion by L. major‐stimulated immune T cells than CD103+ DCs. We next developed CD11c‐diptheria toxin receptor: Batf3−/− mixed bone marrow chimeras to determine when the DCs are important for the control of infection. Mice depleted of Batf‐3‐dependent DCs from day 17 or wild‐type mice depleted of cross‐presenting DCs from 17–19 days after infection maintained significantly larger lesions similar to mice whose Batf‐3‐dependent DCs were depleted from the onset of infection. Thus, we have identified a crucial role for Batf‐3‐dependent DCs in protection against L. major.