{"doi":"10.1016/j.chom.2025.05.015","title":"Interferon-epsilon, an estrogen-induced type I interferon, is uniquely exploited by Neisseria gonorrhoeae via effects on sialic acid metabolism","abstract":"The female genital mucosa expresses the hormone-dependent type I interferon (IFN), IFN-epsilon (IFN-ε), which protects against chlamydia and herpes infection. Surprisingly, we found that IFN-ε knockout ( Ifnε −/− ) mice and type I IFN receptor knockout ( Ifnar1 −/− ) mice exhibited enhanced clearance of Neisseria gonorrhoeae ( Ng ). This result was phenocopied using blocking anti-IFNAR monoclonal antibody (mAb). Ng colonization of the Ifnε −/− urogenital tract was restored by exogenous recombinant IFN-ε or IFN-β. Clearance of Ng in anti-IFNAR-treated mice required the expression of the cathelicidin mCRAMP. Ng deploys a unique mechanism to evade cathelicidins and other innate defenses by sialylating its lipooligosaccharide (LOS) using host-derived cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac or CMP-sialic acid). Ifnε −/− mice expressed reduced levels of CMP-sialic acid synthetase mRNA in genital tissues. Accordingly, Ng recovered from IFN-deficient mice were hyposialylated. In conclusion, Ng exploits type I IFNs to obtain CMP-sialic acid for LOS sialylation, resulting in innate immune evasion and enhanced colonization.","journal":"Cell Host & Microbe","year":2025,"id":523585,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":408016,"name":"Sunita Gulati","orcid":null,"position":1,"is_corresponding":false},{"id":407653,"name":"Michael R. King","orcid":"0000-0002-0223-7808","position":2,"is_corresponding":false},{"id":1396511,"name":"Rosane B. de Oliveira","orcid":null,"position":3,"is_corresponding":false},{"id":408020,"name":"Peter A. Rice","orcid":null,"position":4,"is_corresponding":false},{"id":406676,"name":"Bo Zheng","orcid":"0000-0002-2237-2898","position":5,"is_corresponding":false},{"id":445820,"name":"Jutamas Shaughnessy","orcid":"0000-0003-0832-9954","position":6,"is_corresponding":false},{"id":488018,"name":"Jennifer L. Edwards","orcid":"0000-0003-3568-0344","position":7,"is_corresponding":false},{"id":350102,"name":"Paul J. Hertzog","orcid":"0000-0002-1373-8472","position":8,"is_corresponding":false},{"id":406677,"name":"Sanjay Ram","orcid":"0000-0003-0058-9532","position":9,"is_corresponding":false},{"id":225476,"name":"Douglas T. Golenbock","orcid":"0000-0002-2447-2358","position":10,"is_corresponding":false},{"id":256461,"name":"Evelyn A. Kurt‐Jones","orcid":"0000-0003-4669-2084","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:50:03.004175Z","pmid":"40494348","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":[]}