{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:32:37Z","timestamp":1793320357798,"version":"4.5.0"},"reference-count":135,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["19\/FFP\/6507"],"award-info":[{"award-number":["19\/FFP\/6507"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205455"],"award-info":[{"award-number":["205455"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Activation of the coagulation cascade is a critical, evolutionarily conserved mechanism that maintains hemostasis by rapidly forming blood clots in response to blood\u2010borne infections and damaged blood vessels. Coagulation is a key component of innate immunity since it prevents bacterial dissemination and can provoke inflammation. The term immunothrombosis describes the process by which the innate immune response drives aberrant coagulation, which can result in a lethal condition termed disseminated intravascular coagulation, often seen in sepsis. In this review, we describe the recently uncovered molecular mechanisms underlying inflammasome\u2010 and STING\u2010driven immunothrombosis induced by bacterial and viral infections, culminating in tissue factor (TF) activation and release. Current anticoagulant therapeutics, while effective, are associated with a life\u2010threatening bleeding risk, requiring the urgent development of new treatments. Targeting immunothrombosis may provide a safer option. Thus, we highlight preclinical tools which target TF and\/or block canonical (NLRP3) or noncanonical (caspase\u201011) inflammasome activation as well as STING\u2010driven TF release and discuss clinically approved drugs which block key immunothrombotic processes and, therefore, may be redeployed as safer anticoagulants.<\/jats:p>","DOI":"10.1002\/eji.202149410","type":"journal-article","created":{"date-parts":[[2022,5,15]],"date-time":"2022-05-15T10:08:02Z","timestamp":1652609282000},"page":"1024-1034","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Innate immune signaling and immunothrombosis: New insights and therapeutic opportunities"],"prefix":"10.1002","volume":"52","author":[{"given":"Tristram A. J.","family":"Ryan","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology Trinity Biomedical Sciences Institute Trinity College Dublin  Dublin 2 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A. J.","family":"O'Neill","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology Trinity Biomedical Sciences Institute Trinity College Dublin  Dublin 2 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050664"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-292094"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02576.x"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e31819bceb1"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309846"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH17-02-0079"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107992"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.6995"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.003"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.11.005"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-199208"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.003"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3345"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94495"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-882993"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048488"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2015432"},{"key":"e_1_2_14_19_1","first-page":"1","article-title":"Interplay between inflammation and thrombosis in cardiovascular pathology","author":"Stark K.","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0288"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1707170"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_2_14_23_1","first-page":"35","article-title":"Interaction of tissue factor and factor VII at the earliest phase of coagulation","volume":"17","author":"Josso F.","year":"1965","journal-title":"Thromb. Diath. Haemorrh. Suppl."},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-259267"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20210522"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.13.6258"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/383073a0"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.5.1583.1583"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0631-9"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.6.1517"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.6.2752"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.2.554.014k17_554_559"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4794"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7368"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.15.5.612"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-205914"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0179OC"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00085"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2016003947"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00362a005"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.9.3270"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13181"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.08.013"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806010200"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66125"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12959-019-0194-8"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1565"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.06.011"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256478"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37252"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-741298"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv007"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.677902"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.007"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.07.007"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10558"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13683"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15541"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107967"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207852200"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1240248"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1240988"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0228-2"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.58"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.016"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.013"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747404"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160027"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003041"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312625"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79100"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.02.004"},{"key":"e_1_2_14_74_1","first-page":"1087","article-title":"The role of type 1 interferons in coagulation induced by Gram\u2010negative bacteria","volume":"135","author":"Yang X.","year":"2020","journal-title":"Blood"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.248"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81660"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070247"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11290"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.7.5067"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.016"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH08-11-0759"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03218-7"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-137901"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-526277"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004360"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.7095"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.21.8227"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.1086\/379724"},{"key":"e_1_2_14_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15012-X"},{"key":"e_1_2_14_90_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-08-0483"},{"key":"e_1_2_14_91_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-210179"},{"key":"e_1_2_14_92_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00817"},{"key":"e_1_2_14_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11568-4"},{"key":"e_1_2_14_94_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14768"},{"key":"e_1_2_14_95_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201129"},{"key":"e_1_2_14_96_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007008"},{"key":"e_1_2_14_97_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005743107"},{"key":"e_1_2_14_98_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141374"},{"key":"e_1_2_14_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101069"},{"key":"e_1_2_14_100_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04421-w"},{"key":"e_1_2_14_101_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315547"},{"key":"e_1_2_14_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103369"},{"key":"e_1_2_14_103_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201707"},{"key":"e_1_2_14_104_1","doi-asserted-by":"crossref","unstructured":"Eltobgy M. Zani A. Kenney A. D. Estfanous S. Kim E. Badr A. Carafice C. C.et\u00a0al. Caspase\u20104\/11 exacerbates disease severity in SARS\u2010CoV\u20102 infection by promoting inflammation and thrombosis. bioRxiv. 2021:2021.09.24.461743","DOI":"10.1101\/2021.09.24.461743"},{"key":"e_1_2_14_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00536-9"},{"key":"e_1_2_14_106_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2295"},{"key":"e_1_2_14_107_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc12764"},{"key":"e_1_2_14_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2015.09.008"},{"key":"e_1_2_14_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep25984"},{"key":"e_1_2_14_110_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0061-0"},{"key":"e_1_2_14_111_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-020-03053-y"},{"key":"e_1_2_14_112_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07119.x"},{"key":"e_1_2_14_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.01.007"},{"key":"e_1_2_14_114_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab447"},{"key":"e_1_2_14_115_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0287-8"},{"key":"e_1_2_14_116_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1806239115"},{"key":"e_1_2_14_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.001"},{"key":"e_1_2_14_118_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3806"},{"key":"e_1_2_14_119_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0277-7"},{"key":"e_1_2_14_120_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0234039"},{"key":"e_1_2_14_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.07.016"},{"key":"e_1_2_14_122_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S280922"},{"key":"e_1_2_14_123_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.06.011"},{"key":"e_1_2_14_124_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb9818"},{"key":"e_1_2_14_125_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801627"},{"key":"e_1_2_14_126_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.05.002"},{"key":"e_1_2_14_127_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25790"},{"key":"e_1_2_14_128_1","unstructured":"O.Uo. Randomised Evaluation of COVID\u201019 Therapy (RECOVERY) 2022 [Available from:https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04381936?term=recovery+covid\u201019+dimethyl+fumarate&draw=2&rank=1."},{"key":"e_1_2_14_129_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1912388"},{"key":"e_1_2_14_130_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.018993"},{"key":"e_1_2_14_131_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.108053"},{"key":"e_1_2_14_132_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021372"},{"key":"e_1_2_14_133_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.08.005"},{"key":"e_1_2_14_134_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2017.01.055"},{"key":"e_1_2_14_135_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201810128"},{"key":"e_1_2_14_136_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-03-0246"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202149410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.202149410","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202149410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T16:00:36Z","timestamp":1692547236000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.202149410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":135,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/eji.202149410"],"URL":"https:\/\/doi.org\/10.1002\/eji.202149410","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,24]]},"assertion":[{"value":"2022-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}