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

This study aimed to determine the mechanism by which TLR4 activation establishes cardiac protection in mice subjected to isoproterenol-induced cardiac injury. We performed Multiome sequencing to determine if this was set up through epigenetic means, which would suggest a mechanism consistent with trained innate immune tolerance. Female 10-wk old wild-type (C57BL/6J) mice were treated with lipopolysaccharide (LPS; 2.5 mg/kg), b-glucan (1 mg/mouse), 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 hearts collected and used for nuclei isolation and Multiome sequencing (10x Genomics). Nuclei from all hearts belonging to the same group were pooled prior to submission.