Exploring Macrophage-Dependent Wound Regeneration During Mycobacterial Infection in Zebrafish

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Bohaud, Candice | Johansen, Matt D. | Varga, Béla | Contreras-López, Rafael | Barthelaix, Audrey | Hamela, Claire | Sapède, Dora | Cloitre, Thierry | Gergely, Csilla | Jorgensen, Christian | Kremer, Laurent | Djouad, Farida

Edité par CCSD ; Frontiers -

International audience. The molecular and cellular mechanisms associated with tissue degradation orregeneration in an infectious context are poorly defined. Herein, we explored the role ofmacrophages in orchestrating either tissue regeneration or degradation in zebrafishembryos pre-infected with the fish pathogen Mycobacterium marinum. Zebrafish wereinoculated with different infectious doses of M. marinum prior to fin resection. While mildinfection accelerated fin regeneration, moderate or severe infection delayed this processby reducing blastemal cell proliferation and impeding tissue morphogenesis. This wascorrelated with impaired macrophage recruitment at the wound of the larvae receivinghigh infectious doses. Macrophage activation characterized, in part, by a high expressionlevel of tnfa was exacerbated in severely infected fish during the early phase of theregeneration process, leading to macrophage necrosis and their complete absence inthe later phase. Our results demonstrate how a mycobacterial infection influences themacrophage response and tissue regenerative processes.

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