Innate signaling within the central nervous system recruits protective neutrophils
Abstract 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 experi...
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doaj-d60c0ab7320849308350694b265d8a2d2021-01-10T12:44:20ZengBMCActa Neuropathologica Communications2051-59602020-01-018111310.1186/s40478-019-0876-2Innate signaling within the central nervous system recruits protective neutrophilsReza Khorooshi0Joanna Marczynska1Ruthe Storgaard Dieu2Vian Wais3Christian Rønn Hansen4Stephanie Kavan5Mads Thomassen6Mark Burton7Torben Kruse8Gill A. Webster9Trevor Owens10Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern DenmarkDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern DenmarkDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern DenmarkDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern DenmarkLaboratory of Radiation Physics, Odense University HospitalInstitute of Clinical Research, Department of Clinical Genetics, University of Southern Denmark, Odense University HospitalInstitute of Clinical Research, Department of Clinical Genetics, University of Southern Denmark, Odense University HospitalInstitute of Clinical Research, Department of Clinical Genetics, University of Southern Denmark, Odense University HospitalInstitute of Clinical Research, Department of Clinical Genetics, University of Southern Denmark, Odense University HospitalInnate ImmunotherapeuticsDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern DenmarkAbstract 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.https://doi.org/10.1186/s40478-019-0876-2Innate signalingPhagocytosisNeutrophilsEAECNS homeostasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Reza Khorooshi Joanna Marczynska Ruthe Storgaard Dieu Vian Wais Christian Rønn Hansen Stephanie Kavan Mads Thomassen Mark Burton Torben Kruse Gill A. Webster Trevor Owens |
spellingShingle |
Reza Khorooshi Joanna Marczynska Ruthe Storgaard Dieu Vian Wais Christian Rønn Hansen Stephanie Kavan Mads Thomassen Mark Burton Torben Kruse Gill A. Webster Trevor Owens Innate signaling within the central nervous system recruits protective neutrophils Acta Neuropathologica Communications Innate signaling Phagocytosis Neutrophils EAE CNS homeostasis |
author_facet |
Reza Khorooshi Joanna Marczynska Ruthe Storgaard Dieu Vian Wais Christian Rønn Hansen Stephanie Kavan Mads Thomassen Mark Burton Torben Kruse Gill A. Webster Trevor Owens |
author_sort |
Reza Khorooshi |
title |
Innate signaling within the central nervous system recruits protective neutrophils |
title_short |
Innate signaling within the central nervous system recruits protective neutrophils |
title_full |
Innate signaling within the central nervous system recruits protective neutrophils |
title_fullStr |
Innate signaling within the central nervous system recruits protective neutrophils |
title_full_unstemmed |
Innate signaling within the central nervous system recruits protective neutrophils |
title_sort |
innate signaling within the central nervous system recruits protective neutrophils |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2020-01-01 |
description |
Abstract 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. |
topic |
Innate signaling Phagocytosis Neutrophils EAE CNS homeostasis |
url |
https://doi.org/10.1186/s40478-019-0876-2 |
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