CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis
Authors list
Samira Tamoutounour Sandrine Henri Hugues Lelouard Béatrice de Bovis Colin de Haar C Janneke van der Woude Andrea M Woltman Yasmin Reyal Dominique Bonnet Dorine Sichien Calum C Bain Allan McI Mowat Caetano Reis e Sousa Lionel F Poulin Bernard Malissen Martin GuilliamsAbstract
Dendritic cells (DCs) and monocyte-derived macrophages (MΦs) are key components of intestinal immunity. However, the lack of surface markers differentiating MΦs from DCs has hampered understanding of their respective functions. Here, we demonstrate that, using CD64 expression, MΦs can be distinguished from DCs in the intestine of both mice and humans. On that basis, we revisit the phenotype of intestinal DCs in the absence of contaminating MΦs and we delineate a developmental pathway in the healthy intestine that leads from newly extravasated Ly-6C(hi) monocytes to intestinal MΦs. We determine how inflammation impacts this pathway and show that T cell-mediated colitis is associated with massive recruitment of monocytes to the intestine and the mesenteric lymph node (MLN). There, these monocytes differentiate into inflammatory MΦs endowed with phagocytic activity and the ability to produce inducible nitric oxide synthase. In the MLNs, inflammatory MΦs are located in the T-cell zone and trigger the induction of proinflammatory T cells. Finally, T cell-mediated colitis develops irrespective of intestinal DC migration, an unexpected finding supporting an important role for MLN-resident inflammatory MΦs in the etiology of T cell-mediated colitis.
Journal details
Journal European Journal of Immunology
Volume 42
Issue number 12
Pages 3150-3166
Publication date
Full text links
Publisher website (DOI) 10.1002/eji.201242847
Europe PubMed Central 22936024
Pubmed 22936024
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