Blood myeloid cells are known to be dysregulated in coronavirus disease 2019(COVID-19),caused by SARS-CoV-2.It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate...Blood myeloid cells are known to be dysregulated in coronavirus disease 2019(COVID-19),caused by SARS-CoV-2.It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate immunity discriminate high-risk patients.Thus,we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14LowCD16High monocytes,accumulation of HLA-DRLow classical monocytes(Human Leukocyte Antigen-DR isotype),and release of massive amounts of calprotectin(S100A8/S100A9)in severe cases.Immature CD10LowCD101-CXCR4+/-neutrophils with an immunosuppressive profile accumulated in the blood and lungs,suggesting emergency myelopoiesis.展开更多
Brain macrophages include microglia in the parenchyma,border-associated macrophages in the meningeal-choroid plexus-perivascular space,and monocyte-derived macrophages that infiltrate the brain under various disease c...Brain macrophages include microglia in the parenchyma,border-associated macrophages in the meningeal-choroid plexus-perivascular space,and monocyte-derived macrophages that infiltrate the brain under various disease conditions.The vast heterogeneity of these cells has been elucidated over the last decade using revolutionary multiomics technologies.As such,we can now start to define these various macrophage populations according to their ontogeny and their diverse functional programs during brain development,homeostasis and disease pathogenesis.In this review,we first outline the critical roles played by brain macrophages during development and healthy aging.We then discuss how brain macrophages might undergo reprogramming and contribute to neurodegenerative disorders,autoimmune diseases,and glioma.Finally,we speculate about the most recent and ongoing discoveries that are prompting translational attempts to leverage brain macrophages as prognostic markers or therapeutic targets for diseases that affect the brain.展开更多
文摘Blood myeloid cells are known to be dysregulated in coronavirus disease 2019(COVID-19),caused by SARS-CoV-2.It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate immunity discriminate high-risk patients.Thus,we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14LowCD16High monocytes,accumulation of HLA-DRLow classical monocytes(Human Leukocyte Antigen-DR isotype),and release of massive amounts of calprotectin(S100A8/S100A9)in severe cases.Immature CD10LowCD101-CXCR4+/-neutrophils with an immunosuppressive profile accumulated in the blood and lungs,suggesting emergency myelopoiesis.
文摘Brain macrophages include microglia in the parenchyma,border-associated macrophages in the meningeal-choroid plexus-perivascular space,and monocyte-derived macrophages that infiltrate the brain under various disease conditions.The vast heterogeneity of these cells has been elucidated over the last decade using revolutionary multiomics technologies.As such,we can now start to define these various macrophage populations according to their ontogeny and their diverse functional programs during brain development,homeostasis and disease pathogenesis.In this review,we first outline the critical roles played by brain macrophages during development and healthy aging.We then discuss how brain macrophages might undergo reprogramming and contribute to neurodegenerative disorders,autoimmune diseases,and glioma.Finally,we speculate about the most recent and ongoing discoveries that are prompting translational attempts to leverage brain macrophages as prognostic markers or therapeutic targets for diseases that affect the brain.