{"doi":"10.1093/jimmun/vkaf283.048","title":"Bacterial polyphosphates impede the macrophage response to infection 2084","abstract":"Abstract Description Sepsis affects ∼50 million people annually, with mortality rates of 20–50%. Host-pathogen interactions are implicated in its etiology but are understudied. Bacterial polyphosphates are metabolites with pleiotropic functions in stress response, virulence and host evasion. Here, we reveal polyphosphate-mediated changes during sepsis. In cecal ligation and puncture (CLP)-induced sepsis, gnotobiotic mice colonized with wild type E. coli showed reduced survival versus mice with polyphosphate kinase-deficient E. coli (38% vs 75%), implying polyphosphates mediate lethality. Moreover, polyphosphates impaired local innate immune responses, altered basal and maximal metabolism (OXPHOS, glycolysis), and dysregulated transcriptional programs of metabolic genes (Ldha, Hk2, Slc2a1, Atp5h) as studied by snRNA-Seq in macrophages. Polyphosphates bound to lactate dehydrogenase and affected its activity. In the serum from patients with sepsis (n = 140) polyphosphate accumulation was highest compared to systemic inflammatory response syndrome (n = 114) and healthy controls (n = 143), and higher in non-survivors of sepsis than survivors. Polyphosphate amounts positively correlated with lactate, an established prognostic marker for sepsis. Notably, in murine CLP sepsis, recombinant exopolyphosphate improved survival and lactate by neutralizing polyphosphates. Our findings elucidate how polyphosphates disrupt macrophage functioning, reprogramming innate immune responses and influencing sepsis outcomes. Funding Sources This work was funded by the National Institutes of Health (R01AI153613 to M.B.) and Deutsche Forschungsgemeinschaft (BO3482/3-3, BO3482/4-1 to M.B.). Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)","journal":"The Journal of Immunology","year":2025,"id":582525,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":1494605,"name":"Julian Röwe","orcid":null,"position":1,"is_corresponding":false},{"id":1494606,"name":"Kevin Brueck","orcid":null,"position":2,"is_corresponding":false},{"id":1213683,"name":"Archana Jayaraman","orcid":"0000-0003-0871-6305","position":3,"is_corresponding":false},{"id":571122,"name":"Johannes Platten","orcid":"0000-0002-8054-5726","position":4,"is_corresponding":false},{"id":818882,"name":"Viola Krenzlin","orcid":null,"position":5,"is_corresponding":false},{"id":1494607,"name":"Asala Al-Janabi","orcid":null,"position":6,"is_corresponding":false},{"id":1417335,"name":"Claudius Witzler","orcid":null,"position":7,"is_corresponding":false},{"id":1494155,"name":"Dilraj Kaur","orcid":"0000-0002-2589-3613","position":8,"is_corresponding":false},{"id":1494608,"name":"Mahil Lambert","orcid":null,"position":9,"is_corresponding":false},{"id":1494156,"name":"Verena Raker","orcid":"0000-0001-7264-0371","position":10,"is_corresponding":false},{"id":1494157,"name":"Sabrina Muecklich","orcid":"0000-0003-1898-2674","position":11,"is_corresponding":false},{"id":279856,"name":"Amrit Mann","orcid":null,"position":12,"is_corresponding":false},{"id":1416824,"name":"Thati Madhusudhan","orcid":"0000-0003-0631-8725","position":13,"is_corresponding":false},{"id":981242,"name":"Volker Dötsch","orcid":"0000-0001-5720-212X","position":14,"is_corresponding":false},{"id":1494158,"name":"Frank Bloos","orcid":"0000-0002-0767-7941","position":15,"is_corresponding":false},{"id":1024242,"name":"Michael Bauer","orcid":"0000-0002-1521-3514","position":16,"is_corresponding":false},{"id":625801,"name":"Stefan Tenzer","orcid":"0000-0003-3034-0017","position":17,"is_corresponding":false},{"id":1322519,"name":"Christoph Reinhardt","orcid":"0000-0001-7002-8533","position":18,"is_corresponding":false},{"id":1494609,"name":"Frano Malinarich","orcid":null,"position":19,"is_corresponding":false},{"id":232297,"name":"Markus Bosmann","orcid":"0000-0003-2773-1033","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","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":[]}