title: IL-12p40/IL-10 Producing preCD8α/Clec9A+ Dendritic Cells Are Induced in Neonates upon Listeria monocytogenes Infection.
abstract: Infection by Listeria monocytogenes (Lm) causes serious sepsis and meningitis leading to mortality in neonates. This work explored the ability of CD11c(high) lineage DCs to induce CD8+ T-cell immune protection against Lm in mice before 7 days of life, a period symbolized by the absence of murine IL-12p70-producing CD11c(high)CD8α+ dendritic cells (DCs). We characterized a dominant functional Batf3-dependent precursor of CD11c(high) DCs that is Clec9A+CD205+CD24+ but CD8α- at 3 days of life. After Lm-OVA infection, these pre-DCs that cross-present Ag display the unique ability to produce high levels of IL-12p40 (not IL-12p70 nor IL-23), which enhances OVA-specific CD8+ T cell response, and regulatory IL-10 that limits OVA-specific CD8+ T cell response. Targeting these neonatal pre-DCs for the first time with a single treatment of anti-Clec9A-OVA antibody in combination with a DC activating agent such as poly(I:C) increased the protection against later exposure to the Lm-OVA strain. Poly(I:C) was shown to induce IL-12p40 production, but not IL-10 by neonatal pre-DCs. In conclusion, we identified a new biologically active precursor of Clec9A+ CD8α- DCs, endowed with regulatory properties in early life that represents a valuable target to augment memory responses to vaccines.
authors.affiliation: Institut d'Immunologie Médicale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Torres
authors.affiliation: Institut d'Immunologie Médicale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Köhler
authors.affiliation: Institut d'Immunologie Médicale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delbauve
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia.
authors.forename: Irina
authors.initials: I
authors.lastname: Caminschi
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Immunology, Monash University, Melbourne, Australia.
authors.forename: Mireille H
authors.initials: MH
authors.lastname: Lahoud
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.affiliation: Institut d'Immunologie Médicale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Flamand
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011971:Receptors, Immunologic / Q000276:immunology; D059467:Transcriptome
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; C529914:Clec9a protein, mouse; D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D016753:Interleukin-10