Batf3‐dependent CD103⁺ dendritic cells are major producers of IL‐12 that drive local Th1 immunity against <i>Leishmania major</i> infection in mice

<jats:p>The role of different DC subsets in priming and maintenance of immunity against <jats:italic>Leishmania major</jats:italic> (<jats:italic>L. major</jats:italic>) infection is debated. The transcription factor basic leucine zipper transcription factor, ATF‐like 3 (Batf3) is essential for the development of mouse CD103<jats:sup>+</jats:sup> DCs and some functions of CD8α<jats:sup>+</jats:sup> DCs. We found that CD103<jats:sup>+</jats:sup> DCs were significantly reduced in the dermis of Batf3‐deficient C57BL/6 mice. <jats:italic>Batf3<jats:sup>−/−</jats:sup></jats:italic> mice developed exacerbated and unresolved cutaneous pathology following a low dose of intradermal <jats:italic>L. major</jats:italic> infection in the ear pinnae. Parasite load was increased 1000‐fold locally and expanded systemically. Batf3 deficiency did not affect <jats:italic>L. major</jats:italic> antigen presentation to T cells, which was directly exerted by CD8α<jats:sup>−</jats:sup> conventional DCs (cDCs) in the skin draining LN. However, CD4<jats:sup>+</jats:sup> T‐cell differentiation in the LN and skin was skewed to nonprotective Treg‐ and Th2‐cell subtypes. CD103<jats:sup>+</jats:sup> DCs are major IL‐12 producers during <jats:italic>L. major</jats:italic> infection. Local Th1 immunity was severely hindered, correlating with impaired IL‐12 production and reduction in CD103<jats:sup>+</jats:sup> DC numbers. Adoptive transfer of WT but not IL‐12p40<jats:italic><jats:sup>−/−</jats:sup></jats:italic> Batf3‐dependent DCs significantly improved anti‐<jats:italic>L. major</jats:italic> response in infected <jats:italic>Batf3<jats:sup>−/−</jats:sup></jats:italic> mice. Our results suggest that IL‐12 production by Batf3‐dependent CD103<jats:sup>+</jats:sup> DCs is crucial for maintenance of local Th1 immunity against <jats:italic>L. major</jats:italic> infection.</jats:p>