Innate immune memory after brain injury drives inflammatory cardiac dysfunction
Besides the local inflammatory immune response in the brain, stroke     also alters systemic immunity. Within the acute and sub-acute phase,     the systemic immune response to stroke has been described in detail     over last decades. The long-term systemic immunological consequences after stroke     are however still elusive. Therefore, a better understanding of these long-lasting chronic effects of     stroke on systemic immunity and its impact on remote organ function     and secondary comorbidities is needed. Here, we used single-cell RNA     sequencing (scRNA-Seq) to investigate the chronic effect of stroke on     the transcriptomic signatures of resident myeloid immune cells in various peripheral     organs remote from the brain, including the lung, heart, liver,     spleen, blood and bone marrow. We observed that monocytes     in peripheral organs and in the bone marrow adopt a pro-inflammatory     phenotype which persists chronically after stroke. Moreover, the     pro-inflammatory profile of monocytes in the bone marrow was transmissible     by BM transplantation to naïve recipients, indicating potentially epigenetically     imprinted chronic innate immune memory after stroke. Indeed, by performing single-nuclei ATAC sequencing, we found that post-stroke myeloid immune memory after stroke is likely mediated by IL-1b-driven mechanisms, and that neutralization of the post-stroke increase in circulating IL-1b prevented myeloid immune memory. Overall design: Three independent mouse single-cell RNA experiments were performed on myeloid cells from different peripheral organs (blood, spleen, heart, lung, liver) and bone marrow, chronically after stroke and control conditions.