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A major limitation in the study of chronic fungal infection has been the lack of suitable animal models where the infection is controlled and yet persists. Pulmonary<jats:italic>Cryptococcus neoformans<\/jats:italic>infection in rats results in a diffuse pneumonitis that resolves without dissemination or scarring except for the persistence of interstitial and subpleural granulomas that harbor viable cryptococci inside macrophages and epithelioid cells. Infected rats are asymptomatic but remain infected for as long as 18 months after inoculation with<jats:italic>C. neoformans<\/jats:italic>. Containment of infection is associated with granuloma formation that can be partially abrogated by glucocorticoid administration. Using this model, we identified several features associated with persistent infection in the rat lung, including (i) localization of<jats:italic>C. neoformans<\/jats:italic>to discrete, well-organized granulomas; (ii) intracellular persistence of<jats:italic>C. neoformans<\/jats:italic>within macrophages and epithelioid cells; (iii) reduced inducible nitric oxide synthase expression by granulomas harboring<jats:italic>C. neoformans<\/jats:italic>; and (iv) reduced antibody responses to cryptococcal polysaccharide. The results show that maintenance of persistent infection is associated with downregulation of both cellular and humoral immune responses.<\/jats:p>","DOI":"10.1128\/iai.68.2.832-838.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:58:18Z","timestamp":1027763898000},"page":"832-838","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":138,"title":["Persistent<i>Cryptococcus neoformans<\/i>Pulmonary Infection in the Rat Is Associated with Intracellular Parasitism, Decreased Inducible Nitric Oxide Synthase Expression, and Altered Antibody Responsiveness to Cryptococcal Polysaccharide"],"prefix":"10.1128","volume":"68","author":[{"given":"David L.","family":"Goldman","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Division of Infectious Diseases,1"},{"name":"<!--label omitted: 2-->Departments of Pediatrics,2"},{"name":"<!--label omitted: 6-->Children's Hospital at Montefiore,6 Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhee C.","family":"Lee","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Pathology,3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aron J.","family":"Mednick","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Medicine,4 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lya","family":"Montella","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Departments of Pediatrics,2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Infectious Diseases,1"},{"name":"<!--label omitted: 4-->Medicine,4 and"},{"name":"<!--label omitted: 5-->Microbiology and Immunology,5 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.7.2291-2296.1991"},{"key":"e_1_3_2_3_2","first-page":"236","article-title":"Primary pulmonary cryptococcosis","volume":"94","author":"Campbell G. 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