{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T19:57:48Z","timestamp":1775678268648,"version":"3.50.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Royal City of Dublin Hospital Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Greater understanding of the immunopathogenesis of tuberculosis is critical for developing novel therapies. Here, we propose that immunothrombosis plays an important role in the immune response to Mycobacterium tuberculosis. This interplay among macrophages, neutrophils, and platelets leads to microthrombosis at the site of infection, trapping the mycobacterium to prevent dissemination. We explore how dysregulated immunothrombosis might contribute to tuberculosis pathogenesis, with excessive microthrombosis driving drug resistance, leading to lung damage and venous thromboembolism. Further research into these poorly understood mechanisms could identify options for host-directed therapies to ameliorate immunothrombosis, with its attendant tissue destruction, and reduce the burden of resistance.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf415","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T11:55:53Z","timestamp":1754049353000},"page":"e596-e599","source":"Crossref","is-referenced-by-count":2,"title":["The Emerging Role of Immunothrombosis in the Control and Pathogenesis of\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3483-1262","authenticated-orcid":false,"given":"Se\u00e1n","family":"Donohue","sequence":"first","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, St James's Hospital, Trinity College Dublin, The University of Dublin"},{"name":"Department of Infectious Diseases, St James's Hospital , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina","family":"Leisching","sequence":"additional","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, St James's Hospital, Trinity College Dublin, The University of Dublin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5313-385X","authenticated-orcid":false,"given":"Joseph","family":"Keane","sequence":"additional","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, St James's Hospital, Trinity College Dublin, The University of Dublin"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"2026031710023811000_jiaf415-B1","volume-title":"Global tuberculosis report 2024","author":"World Health Organization","year":"2024"},{"key":"2026031710023811000_jiaf415-B2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/1471-2458-10-259","article-title":"Pulmonary impairment after tuberculosis and its contribution to TB burden","volume":"10","author":"Pasipanodya","year":"2010","journal-title":"BMC Public Health"},{"key":"2026031710023811000_jiaf415-B3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"Engelmann","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"2026031710023811000_jiaf415-B4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41577-021-00536-9","article-title":"Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19","volume":"21","author":"Bonaventura","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"2026031710023811000_jiaf415-B5","first-page":"413","volume-title":"Mechanism of hypersensitivity: the pathogenesis of tuberculosis","author":"Rich","year":"1951","edition":"2nd ed"},{"key":"2026031710023811000_jiaf415-B6","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1007\/s11239-020-02211-7","article-title":"Global epidemiology of venous thromboembolism in people with active tuberculosis: a systematic review and meta-analysis","volume":"51","author":"Danwang","year":"2021","journal-title":"J Thromb Thrombolysis"},{"key":"2026031710023811000_jiaf415-B7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3947\/ic.2019.51.2.142","article-title":"Thromboembolism in Mycobacterium tuberculosis infection: analysis and literature review","volume":"51","author":"Ha","year":"2019","journal-title":"Infect Chemother"},{"key":"2026031710023811000_jiaf415-B8","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.chest.2017.11.029","article-title":"Hemostasis and lipoprotein indices signify exacerbated lung injury in TB with diabetes comorbidity","volume":"153","author":"Dong","year":"2018","journal-title":"Chest"},{"key":"2026031710023811000_jiaf415-B9","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.jinf.2014.10.006","article-title":"Pulmonary tuberculosis induces a systemic hypercoagulable state","volume":"70","author":"Kager","year":"2015","journal-title":"J Infect"},{"key":"2026031710023811000_jiaf415-B10","doi-asserted-by":"crossref","first-page":"6320","DOI":"10.1038\/s41467-022-33796-7","article-title":"Von Willebrand factor links primary hemostasis to innate immunity","volume":"13","author":"Drakeford","year":"2022","journal-title":"Nat Commun"},{"key":"2026031710023811000_jiaf415-B11","doi-asserted-by":"crossref","first-page":"e45700","DOI":"10.1371\/journal.pone.0045700","article-title":"Mycobacterium tuberculosis infection and tissue factor expression in macrophages","volume":"7","author":"Kothari","year":"2012","journal-title":"PLoS One"},{"key":"2026031710023811000_jiaf415-B12","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/eji.201545817","article-title":"Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection","volume":"46","author":"Venkatasubramanian","year":"2016","journal-title":"Eur J Immunol"},{"key":"2026031710023811000_jiaf415-B13","doi-asserted-by":"crossref","first-page":"e114141","DOI":"10.1371\/journal.pone.0114141","article-title":"Role of tissue factor in Mycobacterium tuberculosis\u2013induced inflammation and disease pathogenesis","volume":"9","author":"Kothari","year":"2014","journal-title":"PLoS One"},{"key":"2026031710023811000_jiaf415-B14","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1128\/IAI.00451-09","article-title":"Fibrinogen regulates the cytotoxicity of mycobacterial trehalose dimycolate but is not required for cell recruitment, cytokine response, or control of mycobacterial infection","volume":"78","author":"Sakamoto","year":"2010","journal-title":"Infect Immun"},{"key":"2026031710023811000_jiaf415-B15","doi-asserted-by":"crossref","first-page":"6657","DOI":"10.1038\/s41467-025-61515-5","article-title":"Plasma proteomics for biomarker discovery in childhood tuberculosis","volume":"16","author":"Fossati","year":"2025","journal-title":"Nat Commun"},{"key":"2026031710023811000_jiaf415-B16","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1164\/rccm.201807-1361OC","article-title":"Spatial network mapping of pulmonary multidrug-resistant tuberculosis cavities using RNA sequencing","volume":"200","author":"Dheda","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2026031710023811000_jiaf415-B17","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1038\/s41564-025-02050-3","article-title":"A single-cell transcriptomic atlas reveals senescence and inflammation in the post-tuberculosis human lung","volume":"10","author":"Sun","year":"2025","journal-title":"Nat Microbiol"},{"key":"2026031710023811000_jiaf415-B18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1159\/000348676","article-title":"Mycobacterium tuberculosis\u2013induced neutrophil extracellular traps activate human macrophages","volume":"5","author":"Braian","year":"2013","journal-title":"J Innate Immun"},{"key":"2026031710023811000_jiaf415-B19","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.3389\/fimmu.2018.03147","article-title":"Imbalance of NET and alpha-1-antitrypsin in tuberculosis patients is related with hyper inflammation and severe lung tissue damage","volume":"9","author":"de Melo","year":"2019","journal-title":"Front Immunol"},{"key":"2026031710023811000_jiaf415-B20","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1164\/rccm.201710-2102OC","article-title":"Platelets regulate pulmonary inflammation and tissue destruction in tuberculosis","volume":"198","author":"Fox","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"2026031710023811000_jiaf415-B21","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1093\/infdis\/jiu355","article-title":"Platelets direct monocyte differentiation into epithelioid-like multinucleated giant foam cells with suppressive capacity upon mycobacterial stimulation","volume":"210","author":"Feng","year":"2014","journal-title":"J Infect Dis"},{"key":"2026031710023811000_jiaf415-B22","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1164\/rccm.201910-2063OC","article-title":"Platelets restrict the oxidative burst in phagocytes and facilitate primary progressive tuberculosis","volume":"202","author":"Scheuermann","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"2026031710023811000_jiaf415-B23","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1164\/rccm.201711-2333OC","article-title":"Drug-penetration gradients associated with acquired drug resistance in patients with tuberculosis","volume":"198","author":"Dheda","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"2026031710023811000_jiaf415-B24","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1164\/rccm.202101-0032OC","article-title":"Micro-computed tomography analysis of the human tuberculous lung reveals remarkable heterogeneity in three-dimensional granuloma morphology","volume":"204","author":"Wells","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"2026031710023811000_jiaf415-B25","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/s41564-024-01913-5","article-title":"Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models","volume":"10","author":"Wang","year":"2025","journal-title":"Nat Microbiol"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf415\/63961048\/jiaf415.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/233\/3\/e596\/63961048\/jiaf415.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/233\/3\/e596\/63961048\/jiaf415.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:02:45Z","timestamp":1773756165000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/233\/3\/e596\/8222706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,8,5]]},"published-print":{"date-parts":[[2026,3,17]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf415","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3,15]]},"published":{"date-parts":[[2025,8,5]]}}}