TLR or NOD receptor signaling skews monocyte fate decision via distinct mechanisms driven by mTOR and miR-155

Monocytes are rapidly recruited to inflamed tissues where they differentiate into monocyte-derived macrophages (mo-mac) or dendritic cells (mo-DC). At infection sites, monocytes encounter a broad range of microbial motifs. How pathogen recognition impacts monocyte fate decision is unclear. Here, we...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 43
Main Authors: Coillard, Alice, Guyonnet, Léa, De Juan, Alba, Cros, Adeline, Segura, Elodie
Format: Journal Article
Language:English
Published: United States 26.10.2021
Subjects:
Humans
Signal Transduction
Toll-Like Receptors - metabolism
TOR Serine-Threonine Kinases
macrophage
monocyte
pathogen
dendritic cell
ISSN:1091-6490, 1091-6490
Online Access:Get more information
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Summary:Monocytes are rapidly recruited to inflamed tissues where they differentiate into monocyte-derived macrophages (mo-mac) or dendritic cells (mo-DC). At infection sites, monocytes encounter a broad range of microbial motifs. How pathogen recognition impacts monocyte fate decision is unclear. Here, we show, using an in vitro model allowing the simultaneous differentiation of human mo-mac and mo-DC, that viruses promote mo-mac while Mycobacteria favor mo-DC differentiation. Mechanistically, we found that pathogen sensing through toll-like receptor (TLR) ligands increases mo-mac differentiation via mTORC1. By contrast, nucleotide-binding oligomerization domain (NOD) ligands favor mo-DC through the induction of TNF-α secretion and miR-155 expression. We confirmed these results in vivo, in mouse skin and by analyzing transcriptomic data from human individuals. Overall, our findings allow a better understanding of the molecular control of monocyte differentiation and of monocyte plasticity upon pathogen sensing.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.2109225118