Immune cell activation (M. Nguyen-Chi)


Immune cell activation
Mai Nguyen-Chi

Innate immunity is at the front line to thwart microorganism invasion. The zebrafish has proven particularly suitable for studying immune response to infections and injury. Thanks to the genetic amenability and transparency of its larvae and embryos, it provides an outstanding opportunity to decipher the dynamics of immune cell activation in infected and damaged tissues. 
Our group uses the zebrafish larvae to unravel how phagocytes differentiate and fight microbes.
Research axes

Axis 1 : Defence mechanisms of phagocytes in response to notochord infections in zebrafish larvae

Recently, we developed a system in which bacteria are inaccessible to immune cells. When injected in the notochord, the axial structure of the developing embryo and larva, bacteria cannot physically interact with phagocytes nor be engulfed, probably due to the thick collagen membrane of the notochord that forms a barrier. We are investigating the molecular mechanisms deployed by phagocytes to control the infection.

Figure 1: Macrophage (red) and neutrophil (green) recruitment to the notochord of zebrafish larvae following Escherichia coli infection. The role of the different phagocyte populations was investigated using fluorescent reporter lines. Transection view of the notochord.

Axis 2 : Dynamique d'activation des macrophages en réponse aux blessures et aux infections chez la larve de zebrafish

Macrophages play a central role during inflammation, immune defense, and participate to tissue repair. Macrophages have the ability to adopt a wide range of phenotypes and functions depending on their environment. This process is called polarized activation. We investigate the dynamics of macrophage polarized activation during wound healing and bacterial infections in the zebrafish.

Figure 2: Macrophages recruitment to the wound following caudal fin transection in zebrafish larvae. Transgenic reporters allow the visualization of activated macrophages using different fluorescent proteins using confocale microscopy.

ANR JCJC 2019 MacrophageDynamics

At the heart of organisms as complex as the human body lie the macrophages. They are present within all the tissues, either resident or patrolling the organism to deal with any dead cells, injury or infections. While they may share common origins and features, they may have different flavours. Despite an historical wealth of knowledge about macrophage flavours and phenotypes in vitro, they are still poorly understood in vivo. To study macrophages, we have chosen a simple model, the transparent zebrafish larva that is ideally suited to live observation of immune cells and possesses high homology with human genes and cell types. Injury of the zebrafish caudal fin fold triggers a transient inflammation, followed by a resolution phase contributing to the complete regeneration of the lost tissue. MacrophageDynamics project aims to 1/ set up original tools to study if and how macrophages switch phenotypes, which so far has proven difficult to observe in vivo, 2/ discover new mechanisms involved in the phenotype switch of macrophages during an inflammatory episode. This project will lead to the discovery of new potential therapeutic approaches to manipulate macrophage response to boost tissue repair.

Logo ImageInLife

European Project ImageInLife 
EU Horizon 2020 MSCA-ITN

Team members involved in the project
Selected Publications

Theme leader

Mai Nguyen-Chi
Research Associate (CRCN) CNRS
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LPHI  Laboratory of Pathogen Host Interactions
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