{"doi":"10.1016/j.celrep.2024.114607","title":"Type I interferon governs immunometabolic checkpoints that coordinate inflammation during Staphylococcal infection","abstract":"Macrophage metabolic plasticity is central to inflammatory programming, yet mechanisms of coordinating metabolic and inflammatory programs during infection are poorly defined. Here, we show that type I interferon (IFN) temporally guides metabolic control of inflammation during methicillin-resistant Staphylococcus aureus (MRSA) infection. We find that staggered Toll-like receptor and type I IFN signaling in macrophages permit a transient energetic state of combined oxidative phosphorylation (OXPHOS) and aerobic glycolysis followed by inducible nitric oxide synthase (iNOS)-mediated OXPHOS disruption. This disruption promotes type I IFN, suppressing other pro-inflammatory cytokines, notably interleukin-1β. Upon infection, iNOS expression peaks at 24 h, followed by lactate-driven Nos2 repression via histone lactylation. Type I IFN pre-conditioning prolongs infection-induced iNOS expression, amplifying type I IFN. Cutaneous MRSA infection in mice constitutively expressing epidermal type I IFN results in elevated iNOS levels, impaired wound healing, vasculopathy, and lung infection. Thus, kinetically regulated type I IFN signaling coordinates immunometabolic checkpoints that control infection-induced inflammation.","journal":"Cell Reports","year":2024,"id":424732,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":323210,"name":"Benjamin Klein","orcid":"0000-0002-3412-5536","position":1,"is_corresponding":false},{"id":326143,"name":"Michael J. McFadden","orcid":"0000-0003-0303-6968","position":2,"is_corresponding":false},{"id":1221727,"name":"Norah K. Judge","orcid":"0009-0005-6746-7494","position":3,"is_corresponding":false},{"id":1221728,"name":"Hannah E. Navarrete","orcid":"0000-0002-9147-9779","position":4,"is_corresponding":false},{"id":996344,"name":"Britton C Michmerhuizen","orcid":"0009-0000-5997-9581","position":5,"is_corresponding":false},{"id":578577,"name":"Dominik Awad","orcid":"0000-0002-7386-2061","position":6,"is_corresponding":false},{"id":580379,"name":"Tracey L. Schultz","orcid":"0009-0008-3133-8756","position":7,"is_corresponding":false},{"id":233181,"name":"Paul W. Harms","orcid":"0000-0002-0802-2883","position":8,"is_corresponding":false},{"id":106340,"name":"Li Zhang","orcid":"0000-0002-0703-7506","position":9,"is_corresponding":false},{"id":520949,"name":"Teresa R. O’Meara","orcid":"0000-0002-8901-0154","position":10,"is_corresponding":false},{"id":288649,"name":"Jonathan Z. Sexton","orcid":"0000-0002-9244-5888","position":11,"is_corresponding":false},{"id":106351,"name":"Costas A. Lyssiotis","orcid":"0000-0001-9309-6141","position":12,"is_corresponding":false},{"id":233184,"name":"J. Michelle Kahlenberg","orcid":"0000-0002-4006-8945","position":13,"is_corresponding":false},{"id":564237,"name":"Mary O’Riordan","orcid":"0000-0001-6014-4637","position":14,"is_corresponding":false},{"id":692228,"name":"Mack B. Reynolds","orcid":"0000-0002-8445-3749","position":0,"is_corresponding":true}],"reference_count":118,"raw_metadata":null,"created_at":"2026-07-19T01:58:21.523756Z","pmid":"39126652","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":[]}