title: Cross-presenting dendritic cells are required for control of Leishmania major infection.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Lausanne, Lausanne, Switzerland.
authors.forename: Devika
authors.initials: D
authors.lastname: Ashok
authors.forename: Steffen
authors.initials: S
authors.lastname: Schuster
authors.forename: Catherine
authors.initials: C
authors.lastname: Ronet
authors.forename: Muriel
authors.initials: M
authors.lastname: Rosa
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mack
authors.forename: Christine
authors.initials: C
authors.lastname: Lavanchy
authors.forename: Silvia F
authors.initials: SF
authors.lastname: Marraco
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fasel
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tacchini-Cottier
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000235:genetics / Q000276:immunology; D017951:Antigen Presentation; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma; D018320:Leishmania major / Q000276:immunology* / Q000378:metabolism; D016773:Leishmaniasis, Cutaneous / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000913:Antibodies, Protozoan; D050976:Basic-Leucine Zipper Transcription Factors; D012097:Repressor Proteins; C533289:SNFT protein, mouse; D007073:Immunoglobulin E; D007371:Interferon-gamma
keywords: Batf-3; CD8α+ dendritic cells; Leishmania major