The Programmed Death-1 Signaling Axis Modulates Inflammation and LV Structure/Function in a Stress-Induced Cardiomyopathy Model

•A single intraperitoneal dose of ISO provokes an acute inflammatory response in the heart that is accompanied by reversible changes in LV structure and function.•Single-cell RNA sequencing reveals that ISO injury elicits a transient increase in expression of multiple inhibitory immune checkpoints genes, including Pdcd1 (PD-1) and Cd274 (PD-L1), predominantly in the cardiac resident innate immune cells, including LYVE1− macrophages and dendritic cells.•Treatment with an anti-PD-L1 antibody results in increased myocardial inflammation after ISO injection, whereas ISO injection in PD-1−/− mice results in increased duration of the inflammatory response, prolonged LV dilation, and LV dysfunction relative to wild-type mice.•In vitro stimulation of peritoneal derived inflammatory cells with necrotic cardiac myocytes increases the percentage of cells expressing PD-1 in macrophages and T cells in a TLR2/TLR4/NF-κB–dependent manner.