Department of Medicine, Division of Infectious Diseases and Immunology
Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Immunology and Infectious Disease | Nervous System Diseases | Virus Diseases | Viruses
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.
CXCL1, CXCR2, HSV, chemokines, encephalitis, migration, neutrophil, viral
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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/).
DOI of Published Version
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
Michael BD, Bricio-Moreno L, Sorensen EW, Miyabe Y, Lian J, Solomon T, Kurt-Jones EA, Luster AD. (2020). Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis. Open Access Articles. https://doi.org/10.1016/j.celrep.2020.108150. Retrieved from https://escholarship.umassmed.edu/oapubs/4351
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