Identification of polarized macrophage subsets in zebrafish
- Institut national de la santé et de la recherche médicale, France
- Centre national de la recherche scientifique, France
- Institut Pasteur, France
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.
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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.
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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Identification of polarized macrophage subsets in zebrafish
eLife 4:e07288.
https://doi.org/10.7554/eLife.07288
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