Toll-like Receptor 4 Induces Trained Innate Immune Tolerance in the Heart in a Model of Stress-induced Cardiomyopathy [ATAC-seq]

This study aimed to determine the mechanism by which TLR4 activation establishes cardiac protection in mice subjected to isoproterenol-induced cardiac injury. We performed bulk ATAC sequencing to determine if this was set up through epigenetic means, which would suggest a mechanism consistent with trained innate immune tolerance. Overall design: Female 10-wk old wild-type (C57BL/6J) mice were treated with lipopolysaccharide (LPS; 2.5 mg/kg), 1 ug recombinant interferon-b1/10 ug recombinant interferon-y (IFN), isoproterenol (ISO; 300 mg/kg), or diluent. Mice were then euthanized 7 days later (n=3/group) with bone marrow aspirates collected and used for bulk ATAC sequencing.