{"doi":"10.1101/2020.02.25.965061","title":"Functional remodeling of lysosomes by type I interferon modifies host defense","abstract":"SUMMARY Organelle remodeling is critical for cellular homeostasis, but host factors that control organelle function during microbial infection remain largely uncharacterized. Here, a genome-scale CRISPR/Cas9 screen in intestinal epithelial cells with the prototypical intracellular bacterial pathogen Salmonella led us to discover that type I interferon (IFN-I) remodels lysosomes. Even in the absence of infection, IFN-I signaling modified the localization, acidification, protease activity and proteomic profile of lysosomes. Proteomic and genetic analyses revealed that multiple IFN-I-stimulated genes including Ifitm3, Slc15a3 , and Cnp contribute to lysosome acidification. IFN-I-dependent lysosome acidification stimulated intracellular Salmonella virulence gene expression, leading to rupture of the Salmonella -containing vacuole and host cell death. Moreover, IFN-I signaling promoted in vivo Salmonella pathogenesis in the intestinal epithelium, where Salmonella initiates infection. Our findings explain how an intracellular bacterial pathogen co-opts epithelial IFN-I signaling. We propose that IFN-I control of lysosome function broadly impacts host defense against diverse viral and microbial pathogens.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123480,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9472,"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":477139,"name":"Abdelrahim Zoued","orcid":"0000-0002-6973-1755","position":1,"is_corresponding":false},{"id":477140,"name":"Xu Liu","orcid":"0000-0002-3314-6511","position":2,"is_corresponding":false},{"id":477141,"name":"Brandon Sit","orcid":"0000-0003-2378-3039","position":3,"is_corresponding":false},{"id":332461,"name":"Matthew K. Waldor","orcid":"0000-0003-1843-7000","position":4,"is_corresponding":false},{"id":477138,"name":"Hailong Zhang","orcid":"0000-0002-4903-010X","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:14:59.547352Z","pmid":null,"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":[]}