{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:45:01Z","timestamp":1787161501141,"version":"build-2736575974"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2012,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Persons with previous extrapulmonary tuberculosis have reduced peripheral blood mononuclear cell cytokine production and CD4\n +<\/jats:sup>\n lymphocytes compared to persons with previous pulmonary tuberculosis or latent tuberculosis infection, but specific defects related to\n Mycobacterium tuberculosis<\/jats:named-content>\n infection of macrophages have not been characterized. The objective of this study was to further characterize the\n in vitro<\/jats:italic>\n immune responses to\n M. tuberculosis<\/jats:named-content>\n infection in HIV-seronegative persons with previous extrapulmonary tuberculosis. Peripheral blood mononuclear cells were isolated from HIV-seronegative persons with previous extrapulmonary tuberculosis (\n n<\/jats:italic>\n = 11), previous pulmonary tuberculosis (\n n<\/jats:italic>\n = 21), latent\n M. tuberculosis<\/jats:named-content>\n infection (\n n<\/jats:italic>\n = 19), and uninfected tuberculosis contacts (\n n<\/jats:italic>\n = 20). Experimental conditions included\n M. tuberculosis<\/jats:named-content>\n -infected macrophages cultured with and without monocyte-depleted peripheral blood mononuclear cells. Concentrations of interleukin 1\u03b2 (IL-1\u03b2), IL-4, IL-6, CXCL8 (IL-8), IL-10, IL-12p70, IL-17, CCL2 (monocyte chemoattractant protein 1), tumor necrosis factor alpha (TNF-\u03b1), and gamma interferon (IFN-\u03b3) were measured by multiplex cytokine array. When\n M. tuberculosis<\/jats:named-content>\n -infected macrophages were cocultured with monocyte-depleted peripheral blood mononuclear cells, IFN-\u03b3 (\n P<\/jats:italic>\n = 0.01), TNF-\u03b1 (\n P<\/jats:italic>\n = 0.04), IL-10 (\n P<\/jats:italic>\n < 0.001), and IL-6 (\n P<\/jats:italic>\n = 0.03) exhibited similar continua of responses, with uninfected persons producing the lowest levels, followed by extrapulmonary tuberculosis cases, pulmonary tuberculosis controls, and persons with latent\n M. tuberculosis<\/jats:named-content>\n infection. A similar pattern was observed with CXCL8 (\n P<\/jats:italic>\n = 0.04), IL-10 (\n P<\/jats:italic>\n = 0.02), and CCL2 (\n P<\/jats:italic>\n = 0.03) when monocyte-depleted peripheral blood mononuclear cells from the four groups were cultured alone. Persons with previous extrapulmonary tuberculosis had decreased production of several cytokines, both at rest and after stimulation with\n M. tuberculosis<\/jats:named-content>\n . Our results suggest that persons who develop extrapulmonary tuberculosis have a subtle global immune defect that affects their response to\n M. tuberculosis<\/jats:named-content>\n infection.\n <\/jats:p>","DOI":"10.1128\/cvi.00221-12","type":"journal-article","created":{"date-parts":[[2012,6,6]],"date-time":"2012-06-06T22:41:43Z","timestamp":1339022503000},"page":"1142-1149","source":"Crossref","is-referenced-by-count":22,"title":["Abnormal Immune Responses in Persons with Previous Extrapulmonary Tuberculosis in an\n In Vitro<\/i>\n Model That Simulates\n In Vivo<\/i>\n Infection with Mycobacterium tuberculosis"],"prefix":"10.1128","volume":"19","author":[{"given":"Christina T.","family":"Fiske","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre S.","family":"de Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi K.","family":"Shintani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros A.","family":"Kalams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Sterling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2012,6,6]]},"reference":[{"key":"key20180919073615_B1","doi-asserted-by":"crossref","first-page":"S221","DOI":"10.1164\/ajrccm.161.supplement_3.ats600","article-title":"Targeted tuberculin testing and treatment of latent tuberculosis infection","volume":"161","author":"American Thoracic Society\/Centers for Disease Control and Prevention","year":"2000","journal-title":"Am. 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