{"doi":"10.1126/sciimmunol.abd2876","title":"IL-22–induced cell extrusion and IL-18–induced cell death prevent and cure rotavirus infection","abstract":"Bacterial flagellin can elicit production of TLR5-mediated IL-22 and NLRC4-mediated IL-18 cytokines that act in concert to cure and prevent rotavirus (RV) infection. This study investigated the mechanism by which these cytokines act to impede RV. Although IL-18 and IL-22 induce each other's expression, we found that IL-18 and IL-22 both impeded RV independently of one another and did so by distinct mechanisms that involved activation of their cognate receptors in intestinal epithelial cells (IEC). IL-22 drove IEC proliferation and migration toward villus tips, which resulted in increased extrusion of highly differentiated IEC that serve as the site of RV replication. In contrast, IL-18 induced cell death of RV-infected IEC thus directly interrupting the RV replication cycle, resulting in spewing of incompetent virus into the intestinal lumen and causing a rapid drop in the number of RV-infected IEC. Together, these actions resulted in rapid and complete expulsion of RV, even in hosts with severely compromised immune systems. These results suggest that a cocktail of IL-18 and IL-22 might be a means of treating viral infections that preferentially target short-lived epithelial cells.","journal":"Science Immunology","year":2020,"id":66911,"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":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.949,"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":354261,"name":"Jun Zou","orcid":"0000-0001-6036-8067","position":1,"is_corresponding":false},{"id":354262,"name":"Zhenda Shi","orcid":"0000-0001-8767-7230","position":2,"is_corresponding":false},{"id":354263,"name":"Benyue Zhang","orcid":"0000-0002-3610-3517","position":3,"is_corresponding":false},{"id":354264,"name":"Lucie Etienne‐Mesmin","orcid":"0000-0001-6104-6043","position":4,"is_corresponding":false},{"id":354265,"name":"Yanling Wang","orcid":"0000-0002-1172-1917","position":5,"is_corresponding":false},{"id":218521,"name":"Xuyan Shi","orcid":"0000-0002-1396-9131","position":6,"is_corresponding":false},{"id":218525,"name":"Feng Shao","orcid":"0000-0002-9562-7791","position":7,"is_corresponding":false},{"id":272050,"name":"Benoît Chassaing","orcid":"0000-0002-4285-769X","position":8,"is_corresponding":false},{"id":231449,"name":"Andrew T. Gewirtz","orcid":"0000-0002-6338-7578","position":9,"is_corresponding":false},{"id":354260,"name":"Zhan Zhang","orcid":"0000-0002-5854-4786","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T21:14:50.590588Z","pmid":"33008915","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":[]}