{"doi":"10.1002/jlb.3hi0220-130","title":"Frontline Science: AMPK regulates metabolic reprogramming necessary for interferon production in human plasmacytoid dendritic cells","abstract":"Plasmacytoid dendritic cells (pDCs) play a crucial role in innate viral immunity as the most potent producers of type I interferons (IFN) in the human body. However, the metabolic regulation of IFN production in such vast quantity remains poorly understood. In this study, AMP-activated protein kinase (AMPK) is strongly implicated as a driver of metabolic reprogramming that the authors and others have observed in pDCs after activation via TLR7/9. Oxygen consumption and mitochondrial membrane potential (MMP) were elevated following stimulation of pDCs with influenza or herpes simplex virus. Blocking these changes using mitochondrial inhibitors abrogated IFN-α production. While it appears that multiple carbon sources can be used by pDCs, blocking pyruvate metabolism had the strongest effect on IFN-α production. Furthermore, we saw no evidence of aerobic glycolysis (AG) during pDC activation and blocking lactate dehydrogenase activity did not inhibit IFN-α. TLR7/9 ligation induces a posttranslational modification in Raptor that is catalyzed by AMPK, and blocking TLR7/9 before virus introduction prevents this change. Finally, it is demonstrated that Dorsomorphin, an AMPK inhibitor, inhibited both IFN-α production and MMP in a dose-dependent manner. Taken together, these data reveal a potential cellular mechanism for the metabolic reprogramming in TLR 7/9-activated pDCs that supports activation and IFN-α production.","journal":"Journal of Leukocyte Biology","year":2020,"id":55678,"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":91,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":288471,"name":"Hannah K. Dewald","orcid":"0000-0003-0886-9301","position":1,"is_corresponding":false},{"id":290270,"name":"Zachary S Rothkopf","orcid":null,"position":2,"is_corresponding":false},{"id":288472,"name":"Sukhwinder Singh","orcid":"0000-0002-7061-0096","position":3,"is_corresponding":false},{"id":288473,"name":"Frank J. Jenkins","orcid":"0000-0002-7856-1428","position":4,"is_corresponding":false},{"id":288474,"name":"Pratik Q. Deb","orcid":"0000-0001-6680-7913","position":5,"is_corresponding":false},{"id":288475,"name":"Saurav De","orcid":"0000-0002-5732-5071","position":6,"is_corresponding":false},{"id":105698,"name":"Betsy Barnes","orcid":"0000-0001-6766-4352","position":7,"is_corresponding":false},{"id":288476,"name":"Patricia Fitzgerald‐Bocarsly","orcid":"0000-0002-7604-3184","position":8,"is_corresponding":false},{"id":288470,"name":"Harry J. Hurley","orcid":"0000-0001-6338-0758","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T21:05:29.672878Z","pmid":"32640499","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":[]}