{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:33:55Z","timestamp":1793277235582,"version":"4.5.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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":["Infect Immun"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Infection with\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus neoformans<\/jats:named-content>\n                    begins when desiccated yeast cells or spores are inhaled and lodge in the alveoli of the lungs. A subset of cryptococcal cells in the lungs differentiate into enlarged cells, referred to as titan cells. Titan cells can be as large as 50 to 100 \u03bcm in diameter and exhibit a number of features that may affect interactions with host immune defenses. To characterize the effect of titan cell formation on the host-pathogen interaction, we utilized a previously described\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>\n                    mutant, the\n                    <jats:italic>gpr4<\/jats:italic>\n                    \u0394\n                    <jats:italic>gpr5<\/jats:italic>\n                    \u0394 mutant, which has minimal titan cell production\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The\n                    <jats:italic>gpr4<\/jats:italic>\n                    \u0394\n                    <jats:italic>gpr5<\/jats:italic>\n                    \u0394 mutant strain had attenuated virulence, a lower CFU, and reduced dissemination compared to the wild-type strain. Titan cell production by the wild-type strain also resulted in increased eosinophil accumulation and decreased phagocytosis in the lungs compared to those with the\n                    <jats:italic>gpr4<\/jats:italic>\n                    \u0394\n                    <jats:italic>gpr5<\/jats:italic>\n                    \u0394 mutant strain. Phagocytosed cryptococcal cells exhibited less viability than nonphagocytosed cells, which potentially explains the reduced cell survival and overall attenuation of virulence in the absence of titan cells. These data show that titan cell formation is a novel virulence factor in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>\n                    that promotes establishment of the initial pulmonary infection and plays a key role in disease progression.\n                  <\/jats:p>","DOI":"10.1128\/iai.00507-12","type":"journal-article","created":{"date-parts":[[2012,8,13]],"date-time":"2012-08-13T22:32:10Z","timestamp":1344897130000},"page":"3776-3785","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":146,"title":["Titan Cell Production Enhances the Virulence of Cryptococcus neoformans"],"prefix":"10.1128","volume":"80","author":[{"given":"Juliet N.","family":"Crabtree","sequence":"first","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura H.","family":"Okagaki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin L.","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Strain","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith N.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3206"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.09.061"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-8-16"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.101.4.907"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","unstructured":"CasadevallAPerfectJR. 1998. 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