{"doi":"10.1101/2020.06.08.141309","title":"Influenza-induced activation of recruited alveolar macrophages during the early inflammatory phase drives lung injury and lethality","abstract":"Abstract Severe respiratory virus infections initiate a robust host immune response that contributes to disease severity. Immunomodulatory strategies that limit virus-initiated inflammation are of critical importance. In this study, we compared the host response to influenza A virus (IAV) infection in susceptible animals (wild-type, WT) to resilient mice ( Vimentin -/- mice). We identified distinct gene expression patterns in recruited monocyte-derived alveolar macrophages (MoAMs) associated with three phases (Infiltrating, Early Inflammatory, Late Inflammatory) that evolve in sequence over the course of IAV infection. We report a core set of pro-inflammatory genes involved in the WT MoAM Early Inflammatory response that is suppressed in Vim -/- MoAMs. Moreover, we identify CEBPB, Jun-AP1, and IRF transcriptions factors as regulators of this attenuated inflammatory response. We performed causal experiments using bone-marrow chimeras to credential that Vim -/- MoAMs with suppressed pro-inflammatory genes confer protection from influenza-induced mortality in WT susceptible mice. Taken together, these data support the notion that vimentin plays a causal role in determining the pro-inflammatory function of recruited MoAMs and drives IAV-induced lung injury.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123748,"datarank":0.2766249334522703,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.06868077928428669,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.06868077928428669,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"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":289276,"name":"Kishore R. Anekalla","orcid":"0000-0002-8366-5782","position":1,"is_corresponding":false},{"id":558423,"name":"Yuan‐Shih Hu","orcid":null,"position":2,"is_corresponding":false},{"id":270773,"name":"Jennifer Davis","orcid":"0000-0003-2380-1321","position":3,"is_corresponding":false},{"id":567195,"name":"Mark Ciesielski","orcid":"0000-0002-8996-2323","position":4,"is_corresponding":false},{"id":456351,"name":"Gaurav Gadhvi","orcid":"0000-0002-4379-2824","position":5,"is_corresponding":false},{"id":289277,"name":"Shang-Yang Chen","orcid":"0000-0002-6864-4713","position":6,"is_corresponding":false},{"id":567987,"name":"Margaret Turner","orcid":null,"position":7,"is_corresponding":false},{"id":557814,"name":"Yuan Cheng","orcid":"0000-0003-4173-293X","position":8,"is_corresponding":false},{"id":242098,"name":"Bria M. Coates","orcid":"0000-0003-4264-5440","position":9,"is_corresponding":false},{"id":232815,"name":"Hiam Abdala‐Valencia","orcid":"0000-0003-3384-5299","position":10,"is_corresponding":false},{"id":20865,"name":"Paul A. Reyfman","orcid":"0000-0002-6435-6001","position":11,"is_corresponding":false},{"id":1699,"name":"Alexander V. Misharin","orcid":"0000-0003-2879-3789","position":12,"is_corresponding":false},{"id":230873,"name":"G. R. Scott Budinger","orcid":"0000-0002-3114-5208","position":13,"is_corresponding":false},{"id":456349,"name":"Deborah R. Winter","orcid":"0000-0003-1806-673X","position":14,"is_corresponding":false},{"id":270775,"name":"Karen M. Ridge","orcid":"0000-0001-7784-0014","position":15,"is_corresponding":false},{"id":557813,"name":"Clarissa M. Koch","orcid":"0000-0002-7424-6009","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:03.403566Z","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":[]}