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 CD11chighlineage 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 CD11chighDCs 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.