Batf3-dependent CD103+ dendritic cells are major producers of IL-12 that drive local Th1 immunity against Leishmania major infection in mice.

ABSTRACT: The role of different DC subsets in priming and maintenance of immunity against Leishmania major (L. major) infection is debated. The transcription factor basic leucine zipper transcription factor, ATF-like 3 (Batf3) is essential for the development of mouse CD103(+) DCs and some functions of CD8?(+) DCs. We found that CD103(+) DCs were significantly reduced in the dermis of Batf3-deficient C57BL/6 mice. Batf3(-/-) mice developed exacerbated and unresolved cutaneous pathology following a low dose of intradermal L. major infection in the ear pinnae. Parasite load was increased 1000-fold locally and expanded systemically. Batf3 deficiency did not affect L. major antigen presentation to T cells, which was directly exerted by CD8?(-) conventional DCs (cDCs) in the skin draining LN. However, CD4(+) T-cell differentiation in the LN and skin was skewed to nonprotective Treg- and Th2-cell subtypes. CD103(+) DCs are major IL-12 producers during L. major infection. Local Th1 immunity was severely hindered, correlating with impaired IL-12 production and reduction in CD103(+) DC numbers. Adoptive transfer of WT but not IL-12p40(-/-) Batf3-dependent DCs significantly improved anti-L. major response in infected Batf3(-/-) mice. Our results suggest that IL-12 production by Batf3-dependent CD103(+) DCs is crucial for maintenance of local Th1 immunity against L. major infection.

SUBMITTER: Martinez-Lopez M 

PROVIDER: S-EPMC4316187 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature