Innate signaling within the central nervous system recruits protective neutrophils
| العنوان: | Innate signaling within the central nervous system recruits protective neutrophils |
|---|---|
| المؤلفون: | Mads Thomassen, Reza Khorooshi, Gill Webster, Joanna Marczynska, Trevor Owens, Torben A Kruse, Christian Rønn Hansen, Ruthe Storgaard Dieu, Vian Wais, Stephanie Kavan, Mark Burton |
| المصدر: | Khorooshi, R, Marczynska, J, Dieu, R S, Wais, V, Hansen, C R, Kavan, S, Thomassen, M, Burton, M, Kruse, T, Webster, G A & Owens, T 2020, ' Innate signaling within the central nervous system recruits protective neutrophils ', Acta Neuropathologica Communications, vol. 8, 2 . https://doi.org/10.1186/s40478-019-0876-2 Acta Neuropathologica Communications Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-13 (2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Chemokine, Encephalomyelitis, Autoimmune, Experimental, Neutrophils, Phagocytosis, Innate signaling, Central nervous system, lcsh:RC346-429, Monocytes, Pathology and Forensic Medicine, CNS homeostasis, Cellular and Molecular Neuroscience, Immune system, medicine, Animals, lcsh:Neurology. Diseases of the nervous system, Neuroinflammation, Mice, Knockout, biology, business.industry, EAE, Research, Multiple sclerosis, Monocyte, Experimental autoimmune encephalomyelitis, Brain, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, medicine.anatomical_structure, Neutrophil Infiltration, Spinal Cord, Immunology, biology.protein, Female, Neurology (clinical), Inflammation Mediators, business, Signal Transduction |
| الوصف: | There is great interest in understanding how the central nervous system (CNS) communicates with the immune system for recruitment of protective responses. Infiltrating phagocytic monocytes and granulocytes are implicated in neuroinflammation in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). To investigate how CNS endogenous signals can be harnessed to promote anti-inflammatory programs, we have used a particulate Toll-like receptor 9 and nucleotide-oligomerization domain 2 bispecific innate ligand (MIS416), to address whether its phagocytosis within the CNS recruits protective myeloid cells. We find that MIS416 injected intrathecally into the cerebrospinal fluid via the cisterna magna induced a local chemokine response that recruited blood-derived monocytes and neutrophils to the CNS. These cells phagocytosed MIS416. The increase in EAE severity normally seen from time of onset did not occur in mice receiving MIS416. This suppression of disease symptoms was dependent on expression of the type I interferon receptor (IFNAR). Transfer of intrathecal MIS416-induced neutrophils suppressed EAE in recipient mice, while monocytes did not transfer protection. MIS416-induced neutrophils showed increased IL-10 expression that was IFNAR1-driven. In contrast to intrathecal administration, intravenous administration of MIS416 led to monocyte but not neutrophil infiltration to the CNS. We thus identify a CNS-intrinsic and -specific phagocytosis-induced recruitment of anti-inflammatory neutrophils that contribute to CNS homeostasis and may have therapeutic potential. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8be08cda36e7589ca5238a4e6caa251 https://findresearcher.sdu.dk:8443/ws/files/162861902/Open_Access_Version.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a8be08cda36e7589ca5238a4e6caa251 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |