Innate immune memory after brain injury drives inflammatory cardiac dysfunction [BMT2]
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: A single-cell RNA experiment was performed on blood and heart myeloid cells from BM-depleted recipient mice that were transplanted with bone marrow cells from stroke or control donors.