{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:55:43Z","timestamp":1740128143491,"version":"3.37.3"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Society of Tropical Medicine\/Burroughs Wellcome Fund"},{"DOI":"10.13039\/100005627","name":"Thrasher Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p><jats:italic>Introduction<\/jats:italic>. Our objective is to understand how HIV infection increases the risk of progression from latent tuberculosis (TB) to active disease. We understand now that immunity is a balance of competing immune responses by multiple cell types. Since T-lymphocyte production of interferon-gamma (IFN-<jats:italic>\u03b3<\/jats:italic>) in response to<jats:italic>Mycobacterium tuberculosis (Mtb<\/jats:italic>) antigens fails to differentiate disease from latent infection, we applied a comprehensive profiling methodology to define immune biomarkers that reliably predict a patient\u2019s TB risk.<jats:italic>Methods<\/jats:italic>. We established a cohort of HIV-infected adults with TB disease from Swaziland. Multiparametric flow cytometry was used to quantify the mycobacterial-specific anti-inflammatory (IL-4 and IL-10) and proinflammatory (IFN-<jats:italic>\u03b3<\/jats:italic>) immune response.<jats:italic>Results<\/jats:italic>. From 12 HIV-infected Swaziland patients with TB disease, the CD4<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup>, Double Negative, and CD56<jats:sup>+<\/jats:sup>CD3<jats:sup>\u2212<\/jats:sup>lymphocytes increase their IL-4\u2009:\u2009IFN-<jats:italic>\u03b3<\/jats:italic>ratio as HIV disease worsens (Spearman<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>r<\/mml:mi><\/mml:mrow><\/mml:math>of \u22120.59; \u22120.59; \u22120.60; and \u22120.59, resp.;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.05<\/mml:mn><\/mml:math>). Similarly, HIV severity is associated with an increased IL-10\u2009:\u2009IFN-<jats:italic>\u03b3<\/jats:italic>ratio (Spearman<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:mi>r<\/mml:mi><\/mml:mrow><\/mml:math>of \u22120.76;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn fontstyle=\"italic\">0.01<\/mml:mn><\/mml:math>).<jats:italic>Conclusion<\/jats:italic>. As HIV disease progresses, both the adaptive and innate branches skew away from an inflammatory and towards anti-inflammatory phenotype.<\/jats:p>","DOI":"10.1155\/2016\/1478340","type":"journal-article","created":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T16:00:53Z","timestamp":1456243253000},"page":"1-6","source":"Crossref","is-referenced-by-count":3,"title":["HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response"],"prefix":"10.1155","volume":"2016","author":[{"given":"Andrew R.","family":"DiNardo","sequence":"first","affiliation":[{"name":"The Global Tuberculosis Program, Texas Children\u2019s Hospital, Immigrant and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Mandalakas","sequence":"additional","affiliation":[{"name":"The Global Tuberculosis Program, Texas Children\u2019s Hospital, Immigrant and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gugu","family":"Maphalala","sequence":"additional","affiliation":[{"name":"National Tuberculosis Reference Laboratory, Swaziland Health Laboratory Services, Ministry of Health, Mbabane, Swaziland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Godwin","family":"Mtetwa","sequence":"additional","affiliation":[{"name":"The Global Tuberculosis Program, Texas Children\u2019s Hospital, Baylor College of Medicine Children\u2019s Foundation-Swaziland, Mbabane, Swaziland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Temhlanga","family":"Mndzebele","sequence":"additional","affiliation":[{"name":"The Global Tuberculosis Program, Texas Children\u2019s Hospital, Baylor College of Medicine Children\u2019s Foundation-Swaziland, Mbabane, Swaziland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piluca","family":"Ustero","sequence":"additional","affiliation":[{"name":"The Global Tuberculosis Program, Texas Children\u2019s Hospital, Baylor College of Medicine Children\u2019s Foundation-Swaziland, Mbabane, Swaziland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makhosazana","family":"Hlatshwayo","sequence":"additional","affiliation":[{"name":"The Global Tuberculosis Program, Texas Children\u2019s Hospital, Baylor College of Medicine Children\u2019s Foundation-Swaziland, Mbabane, Swaziland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily M.","family":"Mace","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Texas Children\u2019s Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan S.","family":"Orange","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Texas Children\u2019s Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Makedonas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Texas Children\u2019s Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1086\/651492"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2004.00758.x"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2299"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2299"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000798"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2013.02.004"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2014.06.009"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2015.07.009"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(14)70884-9"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1038\/nri3476"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003304"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1023\/b:viru.0000012260.32578.72"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004603"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201061"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091473"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201003-0334OC"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3230"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003735"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201243262"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1126\/science.8023143"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-125"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1126\/science.8023142"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199709000-00005"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12121"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007394107"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.12.023"}],"container-title":["Mediators 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