{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:07:45Z","timestamp":1790208465765,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2012,5,8]],"date-time":"2012-05-08T00:00:00Z","timestamp":1336435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2012,7,2]],"date-time":"2012-07-02T00:00:00Z","timestamp":1341187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2012,7,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Cryptococcosis is caused by the opportunistic pathogen\n Cryptococcus neoformans<\/jats:named-content>\n or by the primary pathogen\n Cryptococcus gattii<\/jats:named-content>\n . Epidemiological studies suggest that patients infected with\n C. gattii<\/jats:named-content>\n mainly present with pulmonary disease, while those infected with\n C. neoformans<\/jats:named-content>\n commonly manifest meningoencephalitis. We compared the pathogenesis of the two species using the\n C. neoformans<\/jats:named-content>\n H99 and\n C. gattii<\/jats:named-content>\n R265 strains in a murine inhalation model.\n C. neoformans<\/jats:named-content>\n grew faster in the brain and caused death by meningoencephalitis, while\n C. gattii<\/jats:named-content>\n grew faster in the lungs and caused death without producing fulminating meningoencephalitis. Despite the consistent failure to recover R265 cells from blood, a fraction of the R265 population was detected in the extrapulmonary organs, including the brain. Upon intravenous (i.v. ) inoculation of 10\n 4<\/jats:sup>\n cells via the tail vein, however,\n C. gattii<\/jats:named-content>\n produced severe meningoencephalitis, demonstrating that\n C. gattii<\/jats:named-content>\n cells can efficiently cross the blood-brain barrier. Interestingly, i.v. inoculation with five cells caused brain infection in only 10% of\n C. gattii<\/jats:named-content>\n -infected mice, compared to 60% of mice infected with\n C. neoformans<\/jats:named-content>\n . In mice that had been initially inoculated via the pulmonary route and subsequently challenged intravenously, a protective effect was observed only in mice infected with\n C. gattii<\/jats:named-content>\n .\n C. neoformans<\/jats:named-content>\n cells grew 10 to 100 times faster than\n C. gattii<\/jats:named-content>\n cells in blood or serum collected from naive mice. The paucity of meningoencephalitis upon inhalation of\n C. gattii<\/jats:named-content>\n , therefore, may be partly due to an unknown factor(s) in the host\u2019s blood coupled with immune protection that reduces dissemination to the brain and fosters lung infection.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n While\n Cryptococcus neoformans<\/jats:named-content>\n is the most common cause of fatal meningoencephalitis, especially in HIV patients,\n Cryptococcus gattii<\/jats:named-content>\n causes disease mainly in non-HIV patients. Clinical studies revealed that most patients infected with\n C. gattii<\/jats:named-content>\n VGII strains have lung infections with minimal brain involvement. Despite extensive clinicopathological studies on cryptococcosis in animal models, only a few have included\n C. gattii<\/jats:named-content>\n . We compared the pathogenesis of the two species in mice using an inhalation model. Similar to infection in humans, even though\n C. gattii<\/jats:named-content>\n can cross the blood-brain barrier, it failed to cause fatal meningoencephalitis but caused fatal lung infection. We show that growth of\n C. gattii<\/jats:named-content>\n in mouse blood is significantly slower than that of\n C. neoformans<\/jats:named-content>\n and that a secondary protective phenomenon, though weak, manifests itself only in\n C. gattii<\/jats:named-content>\n infection. Our study provides a model for understanding the clinicopathological differences between these two closely genetically related pathogens.\n <\/jats:p>","DOI":"10.1128\/mbio.00103-12","type":"journal-article","created":{"date-parts":[[2012,5,8]],"date-time":"2012-05-08T21:41:11Z","timestamp":1336513271000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":124,"title":["The Primary Target Organ of Cryptococcus gattii Is Different from That of Cryptococcus neoformans in a Murine Model"],"prefix":"10.1128","volume":"3","author":[{"given":"Popchai","family":"Ngamskulrungroj","sequence":"first","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA"},{"name":"Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chang","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Sionov","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung J.","family":"Kwon-Chung","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/00275514.1976.12019972"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.39.2.155.168"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2307\/1555045"},{"key":"e_1_3_2_5_2","first-page":"595","volume-title":"Cryptococcus: from human pathogen to model yeast","author":"Sorrell TC","year":"2010","unstructured":"SorrellTC ChenSCA PhillipsP MarrKA . 2010. Clinical perspectives on Cryptococcus neoformans and Cryptococcus gattii: implications for diagnosis and management, p 595\u2013606. In HeitmanJ KozelTR Kwon-ChungKJ PerfectJR CasadevallA , Cryptococcus: from human pathogen to model yeast. ASM Press, Washington, DC."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-147-4-891"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2006.00088.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780902953886"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0902.020246"},{"key":"e_1_3_2_10_2","volume-title":"Cryptococcus: from human pathogen to model yeast","author":"Meyer W","year":"2011","unstructured":"MeyerW . 2011. Molecular typing of the Cryptococcus neoformans\/C. gattii species complex, p 620. In HeitmanJ KozelTR Kwon-ChungJ PerfectJR CasadevallA , Cryptococcus: from human pathogen to model yeast. 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