CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis

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 Guilliams

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3150-66
Number of pages17
JournalEuropean Journal of Immunology
Volume42
Issue number12
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Animals
  • Antigens, Ly
  • Cell Differentiation
  • Colitis
  • Dendritic Cells
  • Humans
  • Immunity, Mucosal
  • Intestinal Mucosa
  • Lymph Nodes
  • Macrophages
  • Mesentery
  • Mice
  • Mice, Knockout
  • Monocytes
  • Receptors, IgG
  • Th1 Cells

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