{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:27:17Z","timestamp":1790839637023,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2001,3,1]],"date-time":"2001-03-01T00:00:00Z","timestamp":983404800000},"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":[[2001,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tuberculous meningitis is characterized by cerebral tissue destruction. Monocytes, pivotal in immune responses to Mycobacterium tuberculosis, secrete matrix metalloproteinase-9 (MMP-9), which facilitates leukocyte migration across the blood-brain barrier, but may cause cerebral injury. In vitro, human monocytic (THP-1) cells infected by live, virulent M. tuberculosis secreted MMP-9 in a dose-dependent manner. At 24 h, MMP-9 concentrations increased 10-fold to 239 \u00b1 75 ng\/ml (p = 0.001 vs controls). MMP-9 mRNA became detectable at 24\u201348 h. In contrast, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene expression and secretion were similar to constitutive levels from controls at 24 h and increased just 5-fold by 48 h. In vivo investigation revealed MMP-9 concentration per leukocyte in cerebrospinal fluid (CSF) from tuberculous meningitis patients (n = 23; median (range), 3.19 (0.19\u201331.00) ng\/ml\/cell) to be higher than that in bacterial (n = 12; 0.23 (0.01\u201318.37) ng\/ml\/cell) or viral meningitis (n = 20; 0.20 (0.04\u201331.00) ng\/ml\/cell; p &amp;lt; 0.01). TIMP-1, which was constitutively secreted into CSF, was not elevated in tuberculous compared with bacterial meningitis or controls. Thus, a phenotype in which MMP-9 activity is relatively unrestricted by TIMP-1 developed both in vitro and in vivo. This is functionally significant, since MMP-9 concentrations per CSF leukocyte (but not TIMP-1 concentrations) were elevated in fatal tuberculous meningitis and in patients with signs of cerebral tissue damage (unconsciousness, confusion, or neurological deficit; p &amp;lt; 0.05). However, MMP-9 activity was unrelated to the severity of systemic illness. In summary, M. tuberculosis-infected monocytic cells develop a matrix-degrading phenotype, which was observed in vivo and relates to clinical signs reflecting cerebral injury in tuberculous meningitis.<\/jats:p>","DOI":"10.4049\/jimmunol.166.6.4223","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:32:32Z","timestamp":1398036752000},"page":"4223-4230","source":"Crossref","is-referenced-by-count":86,"title":["Identification of a Matrix-Degrading Phenotype in Human Tuberculosis In Vitro and In Vivo"],"prefix":"10.1093","volume":"166","author":[{"given":"Nicholas M","family":"Price","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Farrar","sequence":"additional","affiliation":[{"name":"Wellcome Trust Clinical Research Unit , Ho Chi Minh City ,","place":["Viet Nam"]},{"name":"Center for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran Thi Hong","family":"Chau","sequence":"additional","affiliation":[{"name":"Center for Tropical Diseases , Ho Chi Minh City ,","place":["Viet Nam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Hoang","family":"Mai","sequence":"additional","affiliation":[{"name":"Center for Tropical Diseases , Ho Chi Minh City ,","place":["Viet Nam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran Tinh","family":"Hien","sequence":"additional","affiliation":[{"name":"Center for Tropical Diseases , Ho Chi Minh City ,","place":["Viet Nam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon S","family":"Friedland","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,3,15]]},"reference":[{"key":"2025032714003255300_R1","first-page":"220","volume-title":"JAMA","year":"1995"},{"key":"2025032714003255300_R2"},{"key":"2025032714003255300_R3","first-page":"25","volume-title":"Am. 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