Astrocyte- and neuron-derived CXCL1 drives neutrophil transmigration and blood-brain barrier permeability in viral encephalitis

Michael, Benedict ORCID: 0000-0002-8693-8926, Bricio-Moreno, Laura, Sorensen, Elizabeth, Miyabe, Yoshishige, Lian, Jeffrey, Solomon, Tom ORCID: 0000-0001-7266-6547, Kurt-Jones, Evelyn and Luster, Andrew (2020) Astrocyte- and neuron-derived CXCL1 drives neutrophil transmigration and blood-brain barrier permeability in viral encephalitis. Cell Reports, 32 (11). 108150-.

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Official URL: http://dx.doi.org/10.1016/j.celrep.2020.108150

Abstract

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-1α, 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.

Item Type:	Article
Uncontrolled Keywords:	Blood-Brain Barrier, Astrocytes, Neurons, Neutrophils, Animals, Mice, Inbred C57BL, Herpesvirus 1, Human, Encephalitis, Viral, Acyclovir, Receptors, Interleukin-8B, Neutrophil Infiltration, Permeability, Female, Chemokine CXCL1, Transendothelial and Transepithelial Migration
Depositing User:	Symplectic Admin
Date Deposited:	02 Oct 2020 08:22
Last Modified:	18 Jan 2023 23:30
DOI:	10.1016/j.celrep.2020.108150
Open Access URL:	https://doi.org/10.1016/j.celrep.2020.108150
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3103317