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

Authors

  • Samira Tamoutounour,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, Marseille, France
    2. INSERM U1104, Marseille, France
    3. CNRS UMR7280, Marseille, France
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    • These authors contributed equally to this work.

  • Sandrine Henri,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, Marseille, France
    2. INSERM U1104, Marseille, France
    3. CNRS UMR7280, Marseille, France
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    • These authors contributed equally to this work.

  • Hugues Lelouard,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, Marseille, France
    2. INSERM U1104, Marseille, France
    3. CNRS UMR7280, Marseille, France
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  • Béatrice de Bovis,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, Marseille, France
    2. INSERM U1104, Marseille, France
    3. CNRS UMR7280, Marseille, France
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  • Colin de Haar,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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  • C. Janneke van der Woude,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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  • Andrea M. Woltman,

    1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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  • Yasmin Reyal,

    1. Haematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute, London, UK
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  • Dominique Bonnet,

    1. Haematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute, London, UK
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  • Dorine Sichien,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Laboratory of Immunoregulation and Mucosal Immunology, Ghent University, Ghent, Belgium
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  • Calum C. Bain,

    1. Centre for Immunology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Scotland
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  • Allan McI. Mowat,

    1. Centre for Immunology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Scotland
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  • Caetano Reis e Sousa,

    1. Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK
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  • Lionel F. Poulin,

    1. Center for Infection and Immunity of Lille, Pasteur Institute of Lille, Lille, France
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  • Bernard Malissen,

    Corresponding author
    1. Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, Marseille, France
    2. INSERM U1104, Marseille, France
    3. CNRS UMR7280, Marseille, France
    • Full correspondence Dr. Bernard Malissen, Centre d'Immunologie de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9, France

      Fax: +33-491269430

      e-mail: bernardm@ciml.univ-mrs.fr

      See accompanying article by De Calisto et al.

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  • Martin Guilliams

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, Marseille, France
    2. INSERM U1104, Marseille, France
    3. CNRS UMR7280, Marseille, France
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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-6Chi 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.

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