Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis
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Authors
Michael, Benedict D.Bricio-Moreno, Laura
Sorensen, Elizabeth W.
Miyabe, Yoshishige
Lian, Jeffrey
Solomon, Tom
Kurt-Jones, Evelyn A.
Luster, Andrew D.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2020-09-15Keywords
CXCL1CXCR2
HSV
chemokines
encephalitis
migration
neutrophil
viral
Amino Acids, Peptides, and Proteins
Cell Biology
Cells
Immunology and Infectious Disease
Nervous System Diseases
Virus Diseases
Viruses
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Show full item recordAbstract
Herpes simplex virus (HSV)-1 encephalitis has significant morbidity partly because of an over-exuberant immune response characterized by leukocyte infiltration into the brain and increased blood-brain barrier (BBB) permeability. Determining the role of specific leukocyte subsets and the factors that mediate their recruitment into the brain is critical to developing targeted immune therapies. In a murine model, we find that the chemokines CXCL1 and CCL2 are induced in the brain following HSV-1 infection. Ccr2 (CCL2 receptor)-deficient mice have reduced monocyte recruitment, uncontrolled viral replication, and increased morbidity. Contrastingly, Cxcr2 (CXCL1 receptor)-deficient mice exhibit markedly reduced neutrophil recruitment, BBB permeability, and morbidity, without influencing viral load. CXCL1 is produced by astrocytes in response to HSV-1 and by astrocytes and neurons in response to IL-1alpha, and it is the critical ligand required for neutrophil transendothelial migration, which correlates with BBB breakdown. Thus, the CXCL1-CXCR2 axis represents an attractive therapeutic target to limit neutrophil-mediated morbidity in HSV-1 encephalitis.Source
Michael BD, Bricio-Moreno L, Sorensen EW, Miyabe Y, Lian J, Solomon T, Kurt-Jones EA, Luster AD. Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis. Cell Rep. 2020 Sep 15;32(11):108150. doi: 10.1016/j.celrep.2020.108150. PMID: 32937134; PMCID: PMC7548103. Link to article on publisher's site
DOI
10.1016/j.celrep.2020.108150Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41562PubMed ID
32937134Related Resources
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Copyright 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2020.108150
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Except where otherwise noted, this item's license is described as Copyright 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).