IL-12p40/IL-10 producing preCD8/Clec9A+ dendritic cells are induced in neonates upon listeria monocytogenes infection

David Torres, Arnaud Kohler, Sandrine Delbauve, Irina Caminschi, Mireille H. Lahoud, Ken Shortman, Veronique Flamand

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    11 Citations (Scopus)

    Abstract

    Infection by Listeria monocytogenes (Lm) causes serious sepsis and meningitis leading to mortality in neonates. This work explored the ability of CD11chigh 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 CD11chighCD8α+ dendritic cells (DCs). We characterized a dominant functional Batf3-dependent precursor of CD11chigh 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.
    Original languageEnglish
    Article number1005561
    Number of pages21
    JournalPLoS Pathogens
    Volume12
    Issue number4
    DOIs
    Publication statusPublished - 13 Apr 2016

    Keywords

    • T cells
    • neonates
    • cytotoxic T cells
    • spleen
    • immune response
    • cell staining
    • flow cytometry
    • cytokines

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