{"doi":"10.1101/2025.05.16.654442","title":"Long-term immune reprogramming of classical monocytes with altered ontogeny mediates enhanced lung injury in sepsis survivors","abstract":"Patients who survive sepsis are predisposed to new hospitalizations for respiratory failure, but the underlying mechanisms are unknown. Using a murine model in which prior sepsis predisposes to enhanced lung injury, we previously discovered that classical monocytes persist in the lungs after long-term recovery from sepsis and exhibit enhanced cytokine expression after secondary challenge with intra-nasal lipopolysaccharide. Here, we hypothesized that immune reprogramming of post-sepsis monocytes and altered ontogeny predispose to enhanced lung injury. Monocyte depletion and/or adoptive transfer was performed three weeks and three months after sepsis. Monocytes from post-sepsis mice were necessary and sufficient for enhanced LPS-induced lung injury and promoted neutrophil degranulation. Prior sepsis enhanced JAK-STAT signaling and AP-1 binding in monocytes and shifted monocytes toward the neutrophil-like monocyte lineage. In human sepsis and/or pneumonia survivors, monocytes were predictive of 90-day mortality and exhibit transcriptional and proteomic neutrophil-like signatures. We conclude that sepsis reprograms monocytes into a pro-inflammatory phenotype and skews bone marrow progenitors and monocytes toward the neutrophil-like lineage, predisposing to neutrophil degranulation and lung injury.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557991,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"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":1458008,"name":"Breanna McBean","orcid":"0000-0002-3822-2085","position":1,"is_corresponding":false},{"id":242216,"name":"Alan P. Boyle","orcid":"0000-0002-2081-1105","position":2,"is_corresponding":false},{"id":1370114,"name":"Brett C. Arenberg","orcid":null,"position":3,"is_corresponding":false},{"id":471317,"name":"Matthias Mack","orcid":"0000-0002-3157-7262","position":4,"is_corresponding":false},{"id":277952,"name":"Bethany B. Moore","orcid":"0000-0003-3051-745X","position":5,"is_corresponding":false},{"id":457141,"name":"Michael W. Newstead","orcid":"0000-0002-2512-6377","position":6,"is_corresponding":false},{"id":1458439,"name":"Yanmei Deng","orcid":null,"position":7,"is_corresponding":false},{"id":51780,"name":"Alexey I. Nesvizhskii","orcid":"0000-0002-2806-7819","position":8,"is_corresponding":false},{"id":372182,"name":"Benjamin H. Singer","orcid":"0000-0002-4721-6920","position":9,"is_corresponding":false},{"id":1430580,"name":"Jennifer Cano","orcid":"0009-0008-1250-902X","position":10,"is_corresponding":false},{"id":266626,"name":"Hallie C. Prescott","orcid":"0000-0002-8442-6724","position":11,"is_corresponding":false},{"id":258441,"name":"Helen S. Goodridge","orcid":"0000-0001-8097-2413","position":12,"is_corresponding":false},{"id":262125,"name":"Rachel L. Zemans","orcid":"0000-0003-3537-9869","position":13,"is_corresponding":false},{"id":502513,"name":"Scott J. Denstaedt","orcid":"0000-0002-9173-5146","position":0,"is_corresponding":true}],"reference_count":121,"raw_metadata":null,"created_at":"2026-07-19T02:55:21.727661Z","pmid":"40475424","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":[]}