{"doi":"10.1093/jimmun/vkaf283.405","title":"A helminth secretory product enhances enteric adenovirus infection independent of tuft cells and type 2 immunity 2493","abstract":"Abstract Description Parasitic worms (helminths) infect nearly 25% of the global population, often establishing long-term residence in the GI tract. Helminths share a striking geographic co-occurrence with certain microbial infections, and clinical data suggest that helminth-colonized people suffer worse outcomes to such infections. In mice, helminths promote norovirus and West Nile virus infection through tuft cell- and IL-4Ra/STAT6-driven type 2 inflammation, which dampens antiviral immunity. To specifically probe helminth-virus interactions at the small intestine (SI) epithelium, we established a co-infection model of H. polygyrus (“Hp”) (parasitic roundworm, long-term residence in SI lumen) and mouse adenovirus 2 (“MAdV2”) (infects SI epithelial cells). Mice infected with MAdV2 alone rapidly cleared the virus, whereas Hp/MAdV2-coinfected animals had 103-105-fold higher titers that persisted for weeks. Interestingly, MAdV2 enhancement by Hp did not require tuft cells or any tested component of type 2 immunity (IL-4Ra, IL-5, IL-25, ST2). Furthermore, viral enhancement was not due to impaired antiviral immunity, as Hp enhanced MAdV2 similarly in WT, Rag2; Il2rg-DKO, and Stat1-KO mice. Instead, helminth-conditioned media promoted MAdV2 infection of epithelial cells in vitro and in vivo. These data prompt the hypothesis that a helminth-secreted product promotes MAdV2 infection independent of tuft cells and type 2 immunity. Funding Sources Supported by NIH/NIAID R21AI182722 (JvM) and a postdoctoral fellowship from the Institute for Translational Immunology, University of Washington (TT). Topic Categories Mucosal and Regional Immunology (MUC)","journal":"The Journal of Immunology","year":2025,"id":582216,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"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":1494309,"name":"Debarati Bhadury","orcid":null,"position":1,"is_corresponding":false},{"id":1064732,"name":"Tyler E. Billipp","orcid":"0009-0008-1460-3458","position":2,"is_corresponding":false},{"id":1494310,"name":"Shealyn O’Connor","orcid":null,"position":3,"is_corresponding":false},{"id":344503,"name":"Jason G. Smith","orcid":"0000-0001-6727-5269","position":4,"is_corresponding":false},{"id":678019,"name":"Jakob von Moltke","orcid":"0000-0003-2894-3353","position":5,"is_corresponding":false},{"id":344277,"name":"Thornton W. Thompson","orcid":"0000-0002-6352-8238","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","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":[]}