{"doi":"10.1016/j.celrep.2025.116202","title":"In vitro protocol demonstrating five functional steps of trained immunity in mice: Implications on biomarker discovery and translational research","abstract":"We developed an in vitro methodology to study trained immunity using murine bone-marrow-derived macrophages stimulated with β-glucan and lipopolysaccharide (LPS). Longitudinal analysis of interleukin (IL)-6 and tumor necrosis factor (TNF) production demonstrates that trained macrophages secrete higher cytokine levels following primary stimulation with β-glucan compared to unstimulated macrophages (step 1). After a resting period, trained macrophages return to basal levels of cytokine production (step 2) but rapidly produce enhanced levels of IL-6 and TNF after secondary stimulation with LPS, compared to macrophages individually stimulated with either β-glucan (step 3) or LPS (step 4) alone. The combined cytokine production of macrophages after single stimulation with β-glucan (stimulus 1) and LPS (stimulus 2) is significantly lower than the cytokine levels produced by trained macrophages sequentially stimulated with both β-glucan and LPS (stimulus 1 + 2) (step 5). These results experimentally reproduce the distinctive functional stages that macrophages undergo during the training process.","journal":"Cell Reports","year":2025,"id":520148,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"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":1389173,"name":"Jana Baranda","orcid":"0000-0002-9060-9228","position":1,"is_corresponding":false},{"id":1231073,"name":"Leticia Pérez‐Rodríguez","orcid":"0000-0002-0311-9643","position":2,"is_corresponding":false},{"id":412299,"name":"Patricia Conde","orcid":"0000-0003-2022-5568","position":3,"is_corresponding":false},{"id":1082903,"name":"Carlos de la Calle‐Fabregat","orcid":"0000-0002-3026-3069","position":4,"is_corresponding":false},{"id":1389731,"name":"Marcos J. Berges-Buxeda","orcid":null,"position":5,"is_corresponding":false},{"id":1389174,"name":"Alexander G. Dimitrov","orcid":"0000-0002-1505-4322","position":6,"is_corresponding":false},{"id":854802,"name":"Javier Arranz","orcid":"0000-0003-0891-1215","position":7,"is_corresponding":false},{"id":1389175,"name":"Sergio Rius‐Rocabert","orcid":"0000-0002-2193-5193","position":8,"is_corresponding":false},{"id":1389176,"name":"Alessia Zotta","orcid":"0000-0002-8274-7671","position":9,"is_corresponding":false},{"id":913443,"name":"Ana Dopazo","orcid":"0000-0002-4910-1684","position":10,"is_corresponding":false},{"id":1389177,"name":"Nikita Poddar","orcid":"0000-0003-3037-5519","position":11,"is_corresponding":false},{"id":314370,"name":"Xuedi Wang","orcid":"0009-0002-0709-8349","position":12,"is_corresponding":false},{"id":646581,"name":"Estanislao Nistal‐Villán","orcid":"0000-0003-2458-8833","position":13,"is_corresponding":false},{"id":225188,"name":"Raphaël Duivenvoorden","orcid":"0000-0003-1446-8336","position":14,"is_corresponding":false},{"id":471571,"name":"Joren C. Madsen","orcid":"0000-0003-2724-1333","position":15,"is_corresponding":false},{"id":225206,"name":"David L. Williams","orcid":"0000-0002-4586-9290","position":16,"is_corresponding":false},{"id":329959,"name":"Dan Hasson","orcid":"0000-0001-7943-1636","position":17,"is_corresponding":false},{"id":105260,"name":"Daniel Lozano‐Ojalvo","orcid":"0000-0002-3524-2929","position":18,"is_corresponding":false},{"id":71133,"name":"Florent Ginhoux","orcid":"0000-0002-2857-7755","position":19,"is_corresponding":false},{"id":225198,"name":"Luke O'neill","orcid":"0000-0002-4333-2748","position":20,"is_corresponding":false},{"id":225199,"name":"Jordi Ochando","orcid":"0000-0001-7037-1681","position":21,"is_corresponding":false},{"id":1389730,"name":"Maria González-Pérez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":null,"created_at":"2026-07-19T02:49:23.618703Z","pmid":"41014560","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":[]}