Role of Macrophages and Microglia in Zebrafish Regeneration.

Susanna R Var,Christine A Byrd-Jacobs

doi:10.3390/ijms21134768

Susanna R Var, Christine A Byrd-Jacobs

Open Access

https://doi.org/10.3390/ijms21134768

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Abstract

Currently, there is no treatment for recovery of human nerve function after damage to the central nervous system (CNS), and there are limited regenerative capabilities in the peripheral nervous system. Since fish are known for their regenerative abilities, understanding how these species modulate inflammatory processes following injury has potential translational importance for recovery from damage and disease. Many diseases and injuries involve the activation of innate immune cells to clear damaged cells. The resident immune cells of the CNS are microglia, the primary cells that respond to infection and injury, and their peripheral counterparts, macrophages. These cells serve as key modulators of development and plasticity and have been shown to be important in the repair and regeneration of structure and function after injury. Zebrafish are an emerging model for studying macrophages in regeneration after injury and microglia in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. These fish possess a high degree of neuroanatomical, neurochemical, and emotional/social behavioral resemblance with humans, serving as an ideal simulator for many pathologies. This review explores literature on macrophage and microglial involvement in facilitating regeneration. Understanding innate immune cell behavior following damage may help to develop novel methods for treating toxic and chronic inflammatory processes that are seen in trauma and disease.

Highlights

The immune system is generally divided into the nonspecific innate and the specific adaptive immune system
The expression of pro-inflammatory macrophages via tumor necrosis factor (TNF)-α after an initial injury in zebrafish is similar to mammals, apparent when pro-inflammatory M1-like macrophages expressing TNFβ, IL-β, IL-6 are attracted to the site of injury to clean up foreign material and debris [88,89,90]
The innate immune cells of the peripheral nervous system share similarities with that of the central nervous system (CNS); it is imperative to understand the functions of both macrophages and microglia and study these two cell types collectively

Summary

Introduction

The immune system is generally divided into the nonspecific innate and the specific adaptive immune system. The innate immune system is a nonspecific, evolutionarily conserved defense strategy, responsible for initiating reactions to eliminate potentially damaging and infectious threats in vertebrates, including fish. Innate immune mechanisms include the recruitment of immune cells such as macrophages and microglia to facilitate the removal of tissues and toxic molecules from the circulation and parenchyma as a result of damage from injury, aging, or necrosis [1,2]. Additional consequences of this response can be harmful or helpful, contributing to further damage or to recovery. This review will focus primarily on the contribution of macrophages and microglia in regeneration in the zebrafish

Overview of Physiological Functions of Macrophages and Microglia

Macrophages and Microglia in Tissue Regeneration in Fish

Translational Studies in Fish and Mammalian Models

Findings

Conclusions