Toll-like receptor 3 orchestrates a conserved mechanism of heart regeneration

Abstract

The human’s heart responds to tissue damage with persistent fibrotic scarring. Unlike humans, zebrafish exhibit the ability to repair cardiac injury and re-grow heart tissue throughout life. Here, we provide novel evidence for toll-like receptor 3 (tlr3) driving cardiac regeneration in zebrafish. Upon cardiac injury, survival is decreased in tlr3-/- fish as compared to wildtype controls. Tlr3-/- zebrafish fail to recruit innate immune cells to the injured ventricle, resulting in impaired DNA repair and transcriptional reprogramming of cardiomyocytes. Mechanistically, we uncover an evolutionary conserved mechanism of tlr3 activation in fibroblasts promoting monocyte migration towards an injured ventricular area. Our data reveal tlr3 as a novel therapeutic target to promote cardiac regeneration.