{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:31:15Z","timestamp":1790937075481,"version":"4.1.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV\/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV\/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64+ monocytes were a marker of increased casp1 expression. Furthermore, IL-1\u03b2, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18R\u03b1 on CD4+ T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes\/macrophages of HIV\/TB patients increases with ineffective T cell\u2013dependent activation of monocytes\/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS.<\/jats:p>","DOI":"10.4049\/jimmunol.1502203","type":"journal-article","created":{"date-parts":[[2016,4,14]],"date-time":"2016-04-14T04:10:06Z","timestamp":1460607006000},"page":"4052-4063","source":"Crossref","is-referenced-by-count":73,"title":["Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome"],"prefix":"10.1093","volume":"196","author":[{"given":"Hong Yien","family":"Tan","sequence":"first","affiliation":[{"name":"Centre of Excellence for Research in AIDS, Faculty of Medicine, University of Malaya , 50603 Kuala Lumpur ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yean Kong","family":"Yong","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Research in AIDS, Faculty of Medicine, University of Malaya , 50603 Kuala Lumpur ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esaki M","family":"Shankar","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Research in AIDS, Faculty of Medicine, University of Malaya , 50603 Kuala Lumpur ,","place":["Malaysia"]},{"name":"Tropical Infectious Diseases Research and Education Center, Department of Medical Microbiology, Faculty of Medicine, University of Malaya , 50603 Kuala Lumpur ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geza","family":"Paukovics","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health , Melbourne, Victoria 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rada","family":"Elleg\u00e5rd","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology, Department of Clinical and Experimental Medicine, Link\u00f6ping University , 58185 Link\u00f6ping ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4524-0177","authenticated-orcid":false,"given":"Marie","family":"Larsson","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology, Department of Clinical and Experimental Medicine, Link\u00f6ping University , 58185 Link\u00f6ping ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeeba","family":"Kamarulzaman","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Research in AIDS, Faculty of Medicine, University of Malaya , 50603 Kuala Lumpur ,","place":["Malaysia"]},{"name":"Infectious Disease Unit, Department of Medicine, University of Malaya Medical Centre , 50603 Kuala Lumpur ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4644-1982","authenticated-orcid":false,"given":"Martyn A","family":"French","sequence":"additional","affiliation":[{"name":"School of Pathology and Laboratory Medicine, University of Western Australia , Nedlands, Western Australia 6009 ,","place":["Australia"]},{"name":"Department of Clinical Immunology, Royal Perth Hospital , Perth, Western Australia 6000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M","family":"Crowe","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health , Melbourne, Victoria 3004 ,","place":["Australia"]},{"name":"Infectious Diseases Unit, Alfred Hospital , Melbourne, Victoria 3004 ,","place":["Australia"]},{"name":"Department 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