{"doi":"10.7554/elife.65762","title":"A sustained type I IFN-neutrophil-IL-18 axis drives pathology during mucosal viral infection","abstract":"Neutrophil responses against pathogens must be balanced between protection and immunopathology. Factors that determine these outcomes are not well-understood. In a mouse model of genital herpes simplex virus-2 (HSV-2) infection, which results in severe genital inflammation, antibody-mediated neutrophil depletion reduced disease. Comparative single-cell RNA-sequencing analysis of vaginal cells against a model of genital HSV-1 infection, which results in mild inflammation, demonstrated sustained expression of interferon-stimulated genes (ISGs) only after HSV-2 infection primarily within the neutrophil population. Both therapeutic blockade of IFNα/β receptor 1 (IFNAR1) and genetic deletion of IFNAR1 in neutrophils concomitantly decreased HSV-2 genital disease severity and vaginal IL-18 levels. Therapeutic neutralization of IL-18 also diminished genital inflammation, indicating an important role for this cytokine in promoting neutrophil-dependent immunopathology. Our study reveals that sustained type I interferon (IFN) signaling is a driver of pathogenic neutrophil responses and identifies IL-18 as a novel component of disease during genital HSV-2 infection.","journal":"eLife","year":2021,"id":167323,"datarank":1.2318753656654593,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.7073992314454871,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.7073992314454871,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":31,"citers_with_citation_signal":27,"citers_with_endowment":27,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE161336"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":565912,"name":"Ying Shiang Lim","orcid":"0000-0002-3271-5583","position":1,"is_corresponding":false},{"id":566573,"name":"Adjoa Cofie","orcid":null,"position":2,"is_corresponding":false},{"id":283784,"name":"Prabhakar S. Andhey","orcid":null,"position":3,"is_corresponding":false},{"id":298669,"name":"Xiaoping Jiang","orcid":"0009-0009-4114-4266","position":4,"is_corresponding":false},{"id":335851,"name":"Jason M. Scott","orcid":null,"position":5,"is_corresponding":false},{"id":405088,"name":"Maria Rita Fabbrizi","orcid":"0000-0002-5156-1575","position":6,"is_corresponding":false},{"id":565913,"name":"Ayşe Naz Ozantürk","orcid":"0000-0002-0187-3642","position":7,"is_corresponding":false},{"id":245890,"name":"Christine T. N. Pham","orcid":"0000-0003-1127-3699","position":8,"is_corresponding":false},{"id":339015,"name":"Regina A. Clemens","orcid":"0000-0001-6932-3893","position":9,"is_corresponding":false},{"id":52958,"name":"Maxim N. Artyomov","orcid":"0000-0002-1133-4212","position":10,"is_corresponding":false},{"id":280633,"name":"Mary C. Dinauer","orcid":"0000-0002-7796-2908","position":11,"is_corresponding":false},{"id":334927,"name":"Haina Shin","orcid":"0000-0002-1014-1451","position":12,"is_corresponding":false},{"id":566572,"name":"Tania Lebratti","orcid":null,"position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-18T23:45:54.042727Z","pmid":"34047696","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":[]}