Exploring Macrophage-Dependent Wound Regeneration During Mycobacterial Infection in Zebrafish

Abstract

The molecular and cellular mechanisms associated with tissue degradation or regeneration in an infectious context are poorly defined. Herein, we explored the role of macrophages in orchestrating either tissue regeneration or degradation in zebrafish embryos pre-infected with the fish pathogen Mycobacterium marinum. Zebrafish were inoculated with different infectious doses of M. marinum prior to fin resection. While mild infection accelerated fin regeneration, moderate or severe infection delayed this process by reducing blastemal cell proliferation and impeding tissue morphogenesis. This was correlated with impaired macrophage recruitment at the wound of the larvae receiving high infectious doses. Macrophage activation characterized, in part, by a high expression level of tnfa was exacerbated in severely infected fish during the early phase of the regeneration process, leading to macrophage necrosis and their complete absence in the later phase. Our results demonstrate how a mycobacterial infection influences the macrophage response and tissue regenerative processes.

Inflammation in Development and Aging: Insights from the Zebrafish Model

“…TNF-α, TNFRSF1, TNFRSF2, TNF-N, CD40L, FASL, and 4-1BBL have all been identified in zebrafish. Zebrafish TNF-α is required for several functions, such as larval fin and spinal cord regeneration [21,51,52], and development of the retina [53], liver [54], and blood vessels [55]. TNF-α promotes oligodendrogenesis after myelin injury in a NF-κB-dependent manner, and zebrafish mutants for myeloid differentiation factor 88 (Myd88), a key adaptor for the activation of NF-κB signaling, result in reduced generation of TNF-α in lesions [44].…”

Turning gray selenium and sublimed sulfur into a nanocomposite to accelerate tissue regeneration by isothermal recrystallization

“…However, excessive reactive oxygen species (ROS) are generated around the wound site parallel to angiogenesis [ 13 ], which leads to blood vessel damage that is not beneficial for tissue regeneration [ 14 ]. At the early stage of tissue regeneration, inflammatory cells, including neutrophils and macrophages, are recruited to the site of the wound [ 15 ] to scavenge microorganisms and necrotic cells [ 16 ], providing a hospitable environment for tissue regeneration [ 17 ]. In contrast, chronic inflammation around the wound damages the proliferation and migration of tissue regeneration-related cells [ 18 ], for instance, chronic inflammation in the wounds of those with diabetes [ 19 ].…”

Induction of IL‐32 in the immune response of keratinocytes to Mycobacterium marinum infection

“…The genomes of M. marinum and Mycobacterium tuberculosis share 85% orthologous regions 23 . Therefore, many experts have used M. marinum as a model for studying mycobacterial infections 24,25 . In the present study, we investigated the immune defence mechanisms of keratinocytes against M. marinum by performing single‐cell RNA sequencing (scRNA‐seq) and bulk RNA sequencing (bRNA‐seq) and subsequent data validation.…”