{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T14:07:42Z","timestamp":1777730862948,"version":"3.51.4"},"reference-count":53,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    High-molecular-weight kininogen (HK) is known to bind lipopolysaccharides (LPS) with high affinity and serves as a crucial LPS carrier in circulation, supporting endotoxemia. However, its role in host defense against Gram-negative bacterial infection remains unclear. Here we demonstrate that HK directly binds to\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    ) via LPS and rapidly localizes to sites of infection. HK-deficient mice (\n                    <jats:italic toggle=\"yes\">Kng<\/jats:italic>\n                    1\n                    <jats:italic toggle=\"yes\">\n                      <jats:sup>\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:sup>\/\u2013<\/jats:sup>\n                    ) showed increased susceptibility to infection, with increased bacterial dissemination, lung injury, and proinflammatory cytokine production. In contrast, endogenous expression of human HK in\n                    <jats:italic toggle=\"yes\">Kng<\/jats:italic>\n                    1\n                    <jats:italic toggle=\"yes\">\n                      <jats:sup>\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:sup>\/\u2013<\/jats:sup>\n                    mice restored survival, limited bacterial spread, and reduced tissue damage. Mechanistically, HK promoted neutrophil antimicrobial responses by enhancing reactive oxygen species production and microbicidal activity. Consistently, liver-specific HK deficiency recapitulated the impaired bacterial clearance and reduced survival upon\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    challenge, highlighting the importance of plasma HK. Together, these findings identify HK as a new soluble pattern recognition molecule that senses\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    invasion and initiates neutrophil-mediated antimicrobial responses, revealing a previously unrecognized protective function of the contact system in innate immunity.\n                  <\/jats:p>","DOI":"10.1177\/17534259251405951","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T16:03:02Z","timestamp":1765900982000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["High-molecular-weight kininogen is a critical component of host defense against\n                    <i>Escherichia coli<\/i>\n                    sepsis"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8067-4771","authenticated-orcid":false,"given":"Aizhen","family":"Yang","sequence":"first","affiliation":[{"name":"Cyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Fourth Hospital of Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8865-9227","authenticated-orcid":false,"given":"Yue","family":"Lu","sequence":"additional","affiliation":[{"name":"Cyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Fourth Hospital of Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3814-9957","authenticated-orcid":false,"given":"Xiaofeng","family":"Yan","sequence":"additional","affiliation":[{"name":"Cyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Fourth Hospital of Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0069-7648","authenticated-orcid":false,"given":"Meinan","family":"Peng","sequence":"additional","affiliation":[{"name":"Cyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Fourth Hospital of Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4929-4885","authenticated-orcid":false,"given":"Miao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Cyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Fourth Hospital of Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5116-9266","authenticated-orcid":false,"given":"Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Cyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Fourth Hospital of Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2017.04.015"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.2717"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12898"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-009-0564-y"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.03.018"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02737657"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.Supplement_4.S689"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108898"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)66724-9"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13194"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12959-015-0048-y"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000448"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801329R"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000063797"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.7.3122"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5349"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.08.284"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00312"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-01-0051"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.223545"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00180-15"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3260657"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8723"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/evan.21887"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161900"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102908"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.214"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112567"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2022.11.011"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00288.2017"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02190-12"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101094"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203253"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-12-0920"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152968"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05568-11"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1645960"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02534.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0398-298"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00966-10"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1127"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2015.07.010"},{"key":"e_1_3_2_46_2","first-page":"165","article-title":"Reactivity of murine and human recombinant LPS-binding protein (LBP) within LPS and gram negative bacteria","volume":"47","author":"Lengacher S","year":"1995","unstructured":"Lengacher S, Jongeneel CV, Le Roy D, et al. Reactivity of murine and human recombinant LPS-binding protein (LBP) within LPS and gram negative bacteria. J Inflamm 1995; 47: 165\u2013172.","journal-title":"J Inflamm"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2022.102603"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101305"},{"key":"e_1_3_2_49_2","first-page":"437","article-title":"Mannose-binding lectin enhances the attachment and phagocytosis of mycobacteria in vitro","volume":"53","author":"Bonar A","year":"2005","unstructured":"Bonar A, Chmiela M, Rudnicka W, et al. Mannose-binding lectin enhances the attachment and phagocytosis of mycobacteria in vitro. Arch Immunol Ther Exp (Warsz) 2005; 53: 437\u2013441.","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0604342"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071164"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2128"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2023.09.027"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114151"}],"container-title":["Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17534259251405951","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17534259251405951","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17534259251405951","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:59:48Z","timestamp":1777460388000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17534259251405951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":53,"alternative-id":["10.1177\/17534259251405951"],"URL":"https:\/\/doi.org\/10.1177\/17534259251405951","relation":{},"ISSN":["1753-4259","1753-4267"],"issn-type":[{"value":"1753-4259","type":"print"},{"value":"1753-4267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"article-number":"17534259251405951"}}