Stroke induces disease-specific myeloid cells in the brain parenchyma and pia

• Published in: Nature communications Vol. 13; no. 1; pp. 945 - 14
• Main Authors: Beuker, Carolin, Schafflick, David, Strecker, Jan-Kolja, Heming, Michael, Li, Xiaolin, Wolbert, Jolien, Schmidt-Pogoda, Antje, Thomas, Christian, Kuhlmann, Tanja, Aranda-Pardos, Irene, A-Gonzalez, Noelia, Kumar, Praveen Ashok, Werner, Yves, Kilic, Ertugrul, Hermann, Dirk M., Wiendl, Heinz, Stumm, Ralf, Meyer zu Hörste, Gerd, Minnerup, Jens
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 13/51; 45/91; 631/250/2504/342/1952; 631/250/371; 692/617/375/534; Aged; Aged, 80 and over; Animals; Brain - cytology; Brain - immunology; Brain - pathology; Brain damage; Brain injury; Compartments; Disease Models, Animal; Female; Gene Knock-In Techniques; Humanities and Social Sciences; Humans; Immune response; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - immunology; Infarction, Middle Cerebral Artery - pathology; Ischemia; Leukocytes; Lipids; Male; Meninges; Mice; Microglia; Microglia - cytology; Microglia - immunology; Middle Aged; multidisciplinary; Myeloid cells; Myeloid Cells - immunology; Neurodegenerative diseases; Neuroinflammatory Diseases - immunology; Neuroinflammatory Diseases - pathology; Parenchyma; Phenotypes; Pia Mater - cytology; Pia Mater - immunology; Pia Mater - pathology; Science; Science (multidisciplinary); Signs and symptoms; Stroke; Therapeutic applications; Therapeutic targets
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28593-1

Inflammation triggers secondary brain damage after stroke. The meninges and other CNS border compartments serve as invasion sites for leukocyte influx into the brain thus promoting tissue damage after stroke. However, the post-ischemic immune response of border compartments compared to brain parenchyma remains poorly characterized. Here, we deeply characterize tissue-resident leukocytes in meninges and brain parenchyma and discover that leukocytes respond differently to stroke depending on their site of residence. We thereby discover a unique phenotype of myeloid cells exclusive to the brain after stroke. These stroke-associated myeloid cells partially resemble neurodegenerative disease-associated microglia. They are mainly of resident microglial origin, partially conserved in humans and exhibit a lipid-phagocytosing phenotype. Blocking markers specific for these cells partially ameliorates stroke outcome thus providing a potential therapeutic target. The injury-response of myeloid cells in the CNS is thus compartmentalized, adjusted to the type of injury and may represent a therapeutic target. How ischaemic stroke affects the brain borders is not fully understood. Here the authors show that a stroke-associated myeloid cell population occurs exclusively in brain parenchyma that shares features with neurodegenerative microglia and blockade of proteins on these cells can ameliorate stroke symptoms.