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

Eur J Immunol. 2015 Jan;45(1):119-29. doi: 10.1002/eji.201444651. Epub 2014 Nov 28.


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 CD8α(+) 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 CD8α(-) 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.

Keywords: Adaptive immune response ⋅ Batf3 ⋅ Dendritic cells ⋅ IL-12 ⋅ Leishmania major.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Basic-Leucine Zipper Transcription Factors / deficiency
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / immunology*
  • CD8 Antigens / genetics
  • CD8 Antigens / immunology
  • Cell Differentiation
  • Dendritic Cells / immunology*
  • Dendritic Cells / parasitology
  • Dendritic Cells / transplantation
  • Gene Expression Regulation
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / immunology*
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology*
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Cutaneous / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Repressor Proteins / deficiency
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / parasitology
  • Th1 Cells / immunology*
  • Th1 Cells / parasitology
  • Th2 Cells / immunology
  • Th2 Cells / parasitology


  • Antigens, CD
  • Basic-Leucine Zipper Transcription Factors
  • CD8 Antigens
  • CD8alpha antigen
  • Integrin alpha Chains
  • Repressor Proteins
  • SNFT protein, mouse
  • alpha E integrins
  • Interleukin-12