M‐CSF‐mediated macrophage development is dominantly inhibited by NOD2 signaling for replenishment of immunogenic dendritic cells

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Chauvin, Camille | Alvarez-Simon, Daniel | Régnier, Paul | Radulovic, Katarina | Boulard, Olivier | Delacre, Myriam | Waldschmitt, Nadine | Peyrin-Biroulet, Laurent | Kluza, Jérôme | Darrasse-Jèze, Guillaume | Chamaillard, Mathias | Poulin, Lionel Franz

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International audience. Despite recent advances, it remains unclear whether monocyte‐derived dendritic cells (moDCs) represent alternative context‐dependent fate in the gut. We found here that Nod2‐ dependent sensing of bacteria lowers the ability of circulating monocytes to respond to M‐CSF for generating moDCs. Such inhibitory effect on monocyte‐to‐macrophage transition was prevented upon blockade of TNF‐α. Recognition of the gut microbiota by Nod2 was sufficient to promote the expansion of moDCs within the colonic mucosa. A competitive bone marrow transplant model further demonstrated that Nod2 promotes the conversion of monocytes into dendritic cells. Equally of importance, tumours with the highest transcript levels of NOD2 were associated with a favorable prognosis and characterized by an enrichment of a gene signature related to moDCs. This study implicates that Nod2‐dependent sensing of the gut microbiota influences monocytic lineage commitment into dendritic cells, which sets the stage for future investigations to achieve accurate outcome prediction in colorectal cancer.

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