Defining mononuclear phagocyte distribution and behaviour in the zebrafish heart

Abstract

Mononuclear phagocytes (MNPs) are recognised as highly plastic, multifunctional cells that influence multiple physiological and pathophysiological states. In the heart, they support homeostatic functions, contribute to disease progression and play multiple roles in reparative and regenerative processes following tissue damage. Understanding the heterogeneous populations of cells that contribute to these diverse functions is crucial to facilitating beneficial, and limiting adverse, cardiac outcomes. However, characterisation of precise populations of cardiac immune cells remains incomplete in vertebrate models capable of endogenous regeneration, such as adult zebrafish. Here, we use a combination of transgenic lines to identify distinct MNPs in the zebrafish heart. We show that larval macrophage populations have different origins and a sub-population of csf1ra expressing cells are maintained on the surface of the adult heart. MNPs are differently distributed in the myocardium, exhibit different behaviours and are distinguished via expression level of csf1ra and mpeg1.1. Following injury, tissue resident macrophages rapidly proliferate potentially contributing to reduced scarring. The adult zebrafish heart contains multiple populations of MNPs that can be defined by existing tools. This new understanding of innate immune cell populations in the heart of adult zebrafish sheds light on the composition of a pro-regenerative cardiac microenvironment.