IL-12p40/IL-10 Producing preCD8α/Clec9A+ Dendritic Cells Are Induced in Neonates upon Listeria monocytogenes Infection

PLoS Pathogens

Irina Caminschi¹  Ken Shortman¹  Véronique Flamand²  Mireille H. Lahoud³  Sandrine Delbauve⁴  Arnaud Köhler⁴  David Torres⁴ 

[1] Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia;Department of Immunology, Monash University, Melbourne, Australia;Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia;Institut d’Immunologie Médicale, Université Libre de Bruxelles, Gosselies, Belgium

关键词: T cells;    Neonates;    Cytotoxic T cells;    Spleen;    Immune response;    Cell staining;    Flow cytometry;    Cytokines;   

DOI  :  10.1371/journal.ppat.1005561

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY