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IL-12p40/IL-10 Producing preCD8α/Clec9A+ Dendritic Cells Are Induced in Neonates upon Listeria monocytogenes Infection.
- Source :
- PLoS Pathogens; 4/13/2016, Vol. 12 Issue 4, p1-21, 21p
- Publication Year :
- 2016
-
Abstract
- Infection by Listeria monocytogenes (Lm) causes serious sepsis and meningitis leading to mortality in neonates. This work explored the ability of CD11c<superscript>high</superscript> lineage DCs to induce CD8<superscript>+</superscript> 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<superscript>high</superscript>CD8α<superscript>+</superscript> dendritic cells (DCs). We characterized a dominant functional Batf3-dependent precursor of CD11c<superscript>high</superscript> DCs that is Clec9A<superscript>+</superscript>CD205<superscript>+</superscript>CD24<superscript>+</superscript> but CD8α<superscript>-</superscript> 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<superscript>+</superscript> T cell response, and regulatory IL-10 that limits OVA-specific CD8<superscript>+</superscript> 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<superscript>+</superscript> CD8α<superscript>-</superscript> DCs, endowed with regulatory properties in early life that represents a valuable target to augment memory responses to vaccines. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 12
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 114506782
- Full Text :
- https://doi.org/10.1371/journal.ppat.1005561