{"doi":"10.4049/jimmunol.2101135","title":"Type I IFN Signaling Is Essential for Preventing IFN-γ Hyperproduction and Subsequent Deterioration of Antibacterial Immunity during Postinfluenza Pneumococcal Infection","abstract":"Abstract Postinfluenza bacterial pneumonia is a significant cause of hospitalization and death in humans. The mechanisms underlying this viral and bacterial synergy remain incompletely understood. Recent evidence indicates that influenza-induced IFNs, particularly type I IFN (IFN-I) and IFN-γ, suppress antibacterial defenses. In this study, we have investigated the relative importance and interplay of IFN-I and IFN-γ pathways in influenza-induced susceptibility to Streptococcus pneumoniae infection. Using gene-deficient mouse models, as well as in vivo blocking Abs, we show that both IFN-I and IFN-γ signaling pathways contribute to the initial suppression of antibacterial immunity; however, IFN-γ plays a dominant role in the disease deterioration, in association with increased TNF-α production and alveolar macrophage (AM) depletion. We have previously shown that IFN-γ impairs AM antibacterial function and thereby acute bacterial clearance. The findings in this study indicate that IFN-γ signaling also impairs AM viability and αβ T cell recruitment during the progression of influenza/S. pneumoniae coinfection. Macrophages insensitive to IFN-γ mice express a dominant-negative mutant IFN-γR in mononuclear phagocytes. Interestingly, macrophages insensitive to IFN-γ mice exhibited significantly improved recovery and survival from coinfection, despite delayed bacterial clearance. Importantly, we demonstrate that IFN-I receptor signaling is essential for preventing IFN-γ hyperproduction and animal death during the progression of postinfluenza pneumococcal pneumonia.","journal":"The Journal of Immunology","year":2022,"id":271835,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":937687,"name":"Shruti Bansal","orcid":null,"position":1,"is_corresponding":false},{"id":672520,"name":"Atul Kumar","orcid":"0000-0002-8217-8181","position":2,"is_corresponding":false},{"id":672521,"name":"Christopher Bauer","orcid":"0000-0002-5652-9582","position":3,"is_corresponding":false},{"id":916170,"name":"Shengjun Shao","orcid":null,"position":4,"is_corresponding":false},{"id":915649,"name":"Md Bashir Uddin","orcid":"0000-0002-0045-9669","position":5,"is_corresponding":false},{"id":673233,"name":"Keer Sun","orcid":null,"position":6,"is_corresponding":false},{"id":369472,"name":"Sunil Palani","orcid":"0000-0002-3990-0343","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T00:27:39.717534Z","pmid":"35705254","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":[]}