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To examine the correlates of human immunity to cryptococcal infection in vivo, we analyzed immune parameters at the site of infection over time and assessed the rate of clearance of infection by serial quantitative cerebrospinal fluid (CSF) fungal cultures in 62 patients in a trial of antifungal therapy for HIV-associated cryptococcal meningitis. CSF IL-6, IFN-\u03b3, TNF-\u03b1, and IL-8 were significantly higher in survivors compared with nonsurvivors. There were negative correlations between log TNF-\u03b1, IFN-\u03b3, and IL-6 levels and baseline cryptococcal CFU. Log IFN-\u03b3, G-CSF, TNF-\u03b1, and IL-6 were correlated positively with the rate of fall in log CFU\/ml CSF\/day. In a linear regression model including antifungal treatment group, baseline CFU, and these cytokines, only treatment group and log IFN-\u03b3 remained independently associated with rate of clearance of infection. The results provide direct in vivo evidence for the importance of quantitative differences in IFN-\u03b3 secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-\u03b3 in the treatment of refractory HIV-associated cryptococcosis.<\/jats:p>","DOI":"10.4049\/jimmunol.174.3.1746","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:29:10Z","timestamp":1398032950000},"page":"1746-1750","source":"Crossref","is-referenced-by-count":134,"title":["IFN-\u03b3 at the Site of Infection Determines Rate of Clearance of Infection in Cryptococcal Meningitis"],"prefix":"10.1093","volume":"174","author":[{"given":"Asna A","family":"Siddiqui","sequence":"first","affiliation":[{"name":"Departments of Infectious Diseases and Immunology, St. George\u2019s Hospital Medical School , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie E","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases and Immunology, St. George\u2019s Hospital Medical School , London ,","place":["United Kingdom"]},{"name":"Faculty of Tropical Medicine, Mahidol University , Bangkok ,","place":["Thailand"]},{"name":"Department of Internal Medicine and Infectious Diseases, University Medical Centre , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vannaporn","family":"Wuthiekanun","sequence":"additional","affiliation":[{"name":"Faculty of Tropical Medicine, Mahidol University , Bangkok ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabbar","family":"Jaffar","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Shattock","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases and Immunology, St. George\u2019s Hospital Medical School , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Irving","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases and Immunology, St. George\u2019s Hospital Medical School , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Sheldon","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases and Immunology, St. George\u2019s Hospital Medical School , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wirongrong","family":"Chierakul","sequence":"additional","affiliation":[{"name":"Faculty of Tropical Medicine, Mahidol University , Bangkok ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Peacock","sequence":"additional","affiliation":[{"name":"Faculty of Tropical Medicine, Mahidol University , Bangkok ,","place":["Thailand"]},{"name":"Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Day","sequence":"additional","affiliation":[{"name":"Faculty of Tropical Medicine, Mahidol University , Bangkok ,","place":["Thailand"]},{"name":"Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J","family":"White","sequence":"additional","affiliation":[{"name":"Faculty of Tropical Medicine, Mahidol University , Bangkok ,","place":["Thailand"]},{"name":"Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S","family":"Harrison","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases and Immunology, St. George\u2019s Hospital Medical School , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,2,1]]},"reference":[{"key":"2026020212222398400_R1","first-page":"955","volume-title":"Clin. 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