{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:48:45Z","timestamp":1791071325541,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"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":[[2008,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Cryptococcus neoformans<\/jats:italic>is an encapsulated opportunistic organism that can undergo phenotypic switching. In this process, the parent smooth colony (SM) switches to a more virulent mucoid colony (MC) variant. The host responses mounted against the SM and MC variants differ, and lower tissue interleukin 10 (IL-10) levels are consistently observed in lungs of MC-infected C57BL\/6 and BALB\/c mice. This suggested different roles of this cytokine in SM and MC infections. The objective of this study was to compare survival rates and characterize the host responses of SM- and MC-infected IL-10-depleted (IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>) mice, which exhibit a Th1-polarized immune response and are considered resistant hosts. As expected, SM-infected IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice survived longer than wild-type mice, whereas MC-infected IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice did not exhibit a survival benefit. Consistent with this observation, we demonstrated marked differences in the inflammatory responses of SM- and MC-infected IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>and wild-type mice. This included a more Th1-polarized inflammatory response with enhanced recruitment of macrophages and natural killer and CD8 cells in MC- than in SM-infected IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>and wild-type mice. In contrast, both SM-infected IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>and wild-type mice exhibited higher recruitment of CD4 cells, consistent with enhanced survival and differences in recruitment and Th1\/Th2 polarization. Lung tissue levels of IL-21, IL-6, IL-4, transforming growth factor beta, IL-12, and gamma interferon were higher in MC-infected IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>and wild-type mice than in SM-infected mice, whereas tumor necrosis factor alpha levels were higher in SM-infected IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice. In conclusion, the MC variant elicits an excessive inflammatory response in a Th1-polarized host environment, and therefore, the outcome is negatively affected by the absence of IL-10.<\/jats:p>","DOI":"10.1128\/iai.00529-08","type":"journal-article","created":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:34:04Z","timestamp":1214872444000},"page":"4322-4331","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Phenotypic Switching in<i>Cryptococcus neoformans<\/i>Contributes to Virulence by Changing the Immunological Host Response"],"prefix":"10.1128","volume":"76","author":[{"given":"Abraham","family":"Guerrero","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina C.","family":"Fries","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"},{"name":"Medicine, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.1.68-74.2003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6445-6455.2001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3601-3609.1999"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100960100549"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2006.10.002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.7.2854-2865.1993"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.7.2930-2939.1994"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/322044"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro732"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050308"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.5.1899-1905.1995"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.4994-5000.1998"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/23.1.82"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/424746"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4225-4237.2000"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.1.89-97.1998"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/314521"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.350-357.2005"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.6076-6083.1999"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13407"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3359-3365.2004"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14967"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838331"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.2.1027"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.13.4.7546779"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.4049\/jimmunol.160.5.2393","volume":"160","year":"1998","unstructured":"Huffnagle, G. 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