title: 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 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.
authors.affiliation: Department of Vascular Biology and Inflammation, CNIC-Fundación Centro Nacional de Investigaciones Cardiovasculares "Carlos III", Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martínez-López
authors.forename: Salvador
authors.initials: S
authors.lastname: Iborra
authors.forename: Ruth
authors.initials: R
authors.lastname: Conde-Garrosa
authors.forename: David
authors.initials: D
authors.lastname: Sancho
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology / Q000637:transplantation; D005786:Gene Expression Regulation; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology
chemical_list: D015703:Antigens, CD; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; C431698:CD8alpha antigen; D039001:Integrin alpha Chains; D012097:Repressor Proteins; C533289:SNFT protein, mouse; C091367:alpha E integrins; D018664:Interleukin-12
keywords: Adaptive immune response ⋅ Batf3 ⋅ Dendritic cells ⋅ IL-12 ⋅ Leishmania major