Self-recruited neutrophils trigger over-activated innate immune response and phenotypic change of cardiomyocytes in fulminant viral myocarditis.

ABSTRACT: Fulminant myocarditis (FM) is a life-threatening inflammatory disease. However, the mechanisms underlying its acute onset are unknown. By dynamic cardiac function measurement, we discovered that the initiation of sudden hemodynamic collapse was on day 4 in the mouse model of FM. Single-cell RNA-sequencing study revealed that healthy cardiomyocytes (CMs) lost their contractile and metabolic function and differentiated into pro-angiogenic and pro-inflammatory CMs. Meanwhile, neutrophils, the most expanded immune cells, exhibited a unique developmental trajectory only after migrating to the heart, where they continuously attracted peripheral neutrophils via Cxcl2/Cxcl3, resulting in the acute accumulation of neutrophils in the heart. Well-differentiated cardiac-infiltrating neutrophils, rathe

SUBMITTER: Li H 

PROVIDER: S-EPMC10564723 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature