{"doi":"10.1016/j.celrep.2020.108150","title":"Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis","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.","journal":"Cell Reports","year":2020,"id":51426,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":157,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":256457,"name":"Laura Bricio-Moreno","orcid":"0000-0002-4956-7142","position":1,"is_corresponding":false},{"id":256458,"name":"Elizabeth W. Sorensen","orcid":"0000-0001-8632-6658","position":2,"is_corresponding":false},{"id":256459,"name":"Yoshishige Miyabe","orcid":"0000-0002-7727-5737","position":3,"is_corresponding":false},{"id":256460,"name":"Jeffrey Lian","orcid":"0000-0001-9470-7864","position":4,"is_corresponding":false},{"id":83868,"name":"Tom Solomon","orcid":"0000-0001-7266-6547","position":5,"is_corresponding":false},{"id":256461,"name":"Evelyn A. Kurt‐Jones","orcid":"0000-0003-4669-2084","position":6,"is_corresponding":false},{"id":256462,"name":"Andrew D. Luster","orcid":"0000-0001-9679-7912","position":7,"is_corresponding":false},{"id":256456,"name":"Benedict Michael","orcid":"0000-0002-8693-8926","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-18T20:40:28.278215Z","pmid":"32937134","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}