Abstract

While the mammalian macrophage phenotypes have been intensively studied in vitro, the dynamic of their phenotypic polarization has never been investigated in live vertebrates. We used the zebrafish as a live model to identify and trail macrophage subtypes. We generated a transgenic line whose macrophages expressing tnfa, a key feature of classically activated (M1) macrophages, express fluorescent proteins Tg(mpeg1:mCherryF/tnfa:eGFP-F). Using 4D-confocal microscopy, we showed that both aseptic wounding and E. coli inoculation triggered macrophage recruitment, some of which started to express tnfa. RT-qPCR on FACS-sorted tnfa+ and tnfa- macrophages showed that they respectively expressed M1 and alternatively activated (M2) mammalian markers. Fate tracing of tnfa+ macrophages during the time-course of inflammation demonstrated that pro-inflammatory macrophages converted into M2-like phenotype during the resolution step. Our results reveal the diversity and plasticity of zebrafish macrophage subsets and underline the similarities with mammalian macrophages proposing a new system to study macrophage functional dynamic.

Article and author information

Author details

  1. Mai Nguyen Chi

    Institut de Médecine Régénérative et Biothérapies, Institut national de la santé et de la recherche médicale, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Béryl Laplace-Builhe

    Institut de Médecine Régénérative et Biothérapies, Institut national de la santé et de la recherche médicale, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Jana Travnickova

    Dynamique des Interactions Membranaires Normales et Pathologiques, Centre national de la recherche scientifique, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Patricia Luz-Crawford

    Institut de Médecine Régénérative et Biothérapies, Institut national de la santé et de la recherche médicale, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Gautier Tejedor

    Institut de Médecine Régénérative et Biothérapies, Institut national de la santé et de la recherche médicale, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Quang Tien Phan

    Dynamique des Interactions Membranaires Normales et Pathologiques, Centre national de la recherche scientifique, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Isabelle Duroux-Richard

    Institut de Médecine Régénérative et Biothérapies, Institut national de la santé et de la recherche médicale, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Jean-Pierre Levraud

    Macrophages et Développement de l'Immunité, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Karima Kissa

    Dynamique des Interactions Membranaires Normales et Pathologiques, Centre national de la recherche scientifique, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Georges Lutfalla

    Dynamique des Interactions Membranaires Normales et Pathologiques, Centre national de la recherche scientifique, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Christian Jorgensen

    Institut de Médecine Régénérative et Biothérapies, Institut national de la santé et de la recherche médicale, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Farida Djouad

    Institut de Médecine Régénérative et Biothérapies, Institut national de la santé et de la recherche médicale, Montpellier, France
    For correspondence
    farida.djouad@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Utpal Banerjee, University of California, Los Angeles, United States

Ethics

Animal experimentation: Ethics statementAll animal experiments described in the present study were conducted at the University Montpellier 2 according to European Union guidelines for handling of laboratory animals (http://ec.europa.eu/environment/chemicals/lab_animals/home_en.htm) and were approved by the Direction Sanitaire et Vétérinaire de l'Hérault and Comité d'Ethique pour l'Expérimentation Animale under reference CEEA-LR-13007.

Version history

  1. Received: March 3, 2015
  2. Accepted: July 7, 2015
  3. Accepted Manuscript published: July 8, 2015 (version 1)
  4. Version of Record published: August 3, 2015 (version 2)

Copyright

© 2015, Nguyen Chi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Mai Nguyen Chi
  2. Béryl Laplace-Builhe
  3. Jana Travnickova
  4. Patricia Luz-Crawford
  5. Gautier Tejedor
  6. Quang Tien Phan
  7. Isabelle Duroux-Richard
  8. Jean-Pierre Levraud
  9. Karima Kissa
  10. Georges Lutfalla
  11. Christian Jorgensen
  12. Farida Djouad
(2015)
Identification of polarized macrophage subsets in zebrafish
eLife 4:e07288.
https://doi.org/10.7554/eLife.07288

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https://doi.org/10.7554/eLife.07288