{"doi":"10.1084/jem.20250049","title":"Factor XII–driven coagulation traps bacterial infections","abstract":"Blood coagulation is essential for stopping bleeding but also drives thromboembolic disorders. Factor XII (FXII)-triggered coagulation promotes thrombosis while being dispensable for hemostasis, making it a potential anticoagulant target. However, its physiological role remains unclear. Here, we demonstrate that FXII-driven coagulation enhances innate immunity by trapping pathogens and restricting bacterial infection in mice. Streptococcus pneumoniae infection was more severe in FXII-deficient (F12-/-) mice, with increased pulmonary bacterial burden, systemic spread, and mortality. Similarly, Staphylococcus aureus skin infections and systemic dissemination were exacerbated in F12-/- mice. Reconstitution with human FXII restored bacterial containment. Plasma kallikrein amplifies FXII activation, and its deficiency aggravated S. aureus skin infections, similarly to F12-/- mice. FXII deficiency impaired fibrin deposition in abscess walls, leading to leaky capsules and bacterial escape. Bacterial long-chain polyphosphate activated FXII, triggering fibrin formation. Deficiency in FXII substrate factor XI or FXII/factor XI co-deficiency similarly exacerbated S. aureus infection. The data reveal a protective role for FXII-driven coagulation in host defense, urging caution in developing therapeutic strategies targeting this pathway.","journal":"The Journal of Experimental Medicine","year":2025,"id":512879,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"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":682569,"name":"Anne Jämsä","orcid":null,"position":1,"is_corresponding":false},{"id":681530,"name":"Sandra Konrath","orcid":"0009-0007-2336-8982","position":2,"is_corresponding":false},{"id":1373095,"name":"Praveen Papareddy","orcid":"0000-0002-3872-478X","position":3,"is_corresponding":false},{"id":681537,"name":"Lynn M. Butler","orcid":"0000-0002-2352-8217","position":4,"is_corresponding":false},{"id":618815,"name":"Evi X. Stavrou","orcid":"0000-0002-6075-7609","position":5,"is_corresponding":false},{"id":618818,"name":"Maike Frye","orcid":"0000-0002-6257-7636","position":6,"is_corresponding":false},{"id":681534,"name":"Mathias Gelderblom","orcid":"0000-0002-4254-3439","position":7,"is_corresponding":false},{"id":295119,"name":"Bernhard Nieswandt","orcid":"0000-0003-1454-7413","position":8,"is_corresponding":false},{"id":957874,"name":"Sven Hammerschmidt","orcid":"0000-0002-6382-6681","position":9,"is_corresponding":false},{"id":1373096,"name":"Heiko Herwald","orcid":"0000-0002-8111-2842","position":10,"is_corresponding":false},{"id":287690,"name":"Thomas Renné","orcid":"0000-0003-4594-5975","position":11,"is_corresponding":false},{"id":1373094,"name":"Katrin F. Nickel","orcid":"0000-0003-1287-6766","position":0,"is_corresponding":true}],"reference_count":109,"raw_metadata":null,"created_at":"2026-07-19T02:48:11.233009Z","pmid":"40261297","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":[]}