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

Abstract : 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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https://www.hal.inserm.fr/inserm-03420662
Contributor : Elodie Segura Connect in order to contact the contributor
Submitted on : Tuesday, November 9, 2021 - 12:21:23 PM
Last modification on : Tuesday, May 31, 2022 - 10:20:18 AM
Long-term archiving on: : Thursday, February 10, 2022 - 6:43:25 PM

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Alice Coillard, Léa Guyonnet, Alba de Juan, Adeline Cros, Elodie Segura. TLR or NOD receptor signaling skews monocyte fate decision via distinct mechanisms driven by mTOR and miR-155. Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2021, 118 (43), pp.e2109225118. ⟨10.1073/pnas.2109225118⟩. ⟨inserm-03420662⟩

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