{"doi":"10.1101/2020.04.16.045054","title":"Immune modulation to improve survival of respiratory virus infections in mice","abstract":"Abstract Viral pneumonia remains a global health threat requiring novel treatment strategies, as strikingly exemplified in the SARS-CoV-2 pandemic of 2019-2020. We have reported that mice treated with a combination of inhaled Toll-like receptor (TLR) 2/6 and TLR 9 agonists (Pam2-ODN) to stimulate innate immunity are broadly protected against respiratory pathogens, but the mechanisms underlying this protection remain incompletely elucidated. Here, we show in a lethal paramyxovirus model that Pam2-ODN-enhanced survival is associated with robust virus inactivation by reactive oxygen species (ROS), which occurs prior to internalization by lung epithelial cells. However, we also found that mortality in sham-treated mice temporally corresponded with CD8 + T cell-enriched lung inflammation that peaks on days 11-12 after viral challenge, when the viral burden has waned to a scarcely detectable level. Pam2-ODN treatment blocked this injurious inflammation by reducing the viral burden, and alternatively, depleting CD8 + T cells 8 days after viral challenge also decreased mortality. These findings reveal opportunities for targeted immunomodulation to protect susceptible individuals against the morbidity and mortality of respiratory viral infections.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124803,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"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":364802,"name":"José R. Flores","orcid":"0000-0003-2942-6147","position":1,"is_corresponding":false},{"id":364803,"name":"Ana M. Jaramillo","orcid":"0000-0001-8089-4275","position":2,"is_corresponding":false},{"id":364801,"name":"David L. Goldblatt","orcid":"0000-0003-3805-3127","position":3,"is_corresponding":false},{"id":297872,"name":"Jezreel Pantaleón García","orcid":"0000-0002-9647-2584","position":4,"is_corresponding":false},{"id":364805,"name":"Michael J. Tuvim","orcid":"0000-0001-8126-7716","position":5,"is_corresponding":false},{"id":252487,"name":"Burton F. Dickey","orcid":"0000-0002-4780-1847","position":6,"is_corresponding":false},{"id":297875,"name":"Scott E. Evans","orcid":"0000-0003-4503-0644","position":7,"is_corresponding":false},{"id":364804,"name":"Shradha Wali","orcid":"0000-0002-6077-7618","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:11.632153Z","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":[]}