{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:36:02Z","timestamp":1792798562854,"version":"4.5.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T00:00:00Z","timestamp":1519084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Pathology Department, University of Utah","award":["Start-up grant"],"award-info":[{"award-number":["Start-up grant"]}],"id":[{"id":"https:\/\/ror.org\/03r0ha626","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS041249"],"award-info":[{"award-number":["R01 NS041249"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n                    is a common environmental yeast and opportunistic pathogen responsible for 15% of AIDS-related deaths worldwide. Mortality primarily results from meningoencephalitis, which occurs when fungal cells disseminate to the brain from the initial pulmonary infection site. A key\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    virulence trait is the polysaccharide capsule. Capsule shields\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    from immune-mediated recognition and destruction. The main capsule component, glucuronoxylomannan (GXM), is found both attached to the cell surface and free in the extracellular space (as exo-GXM). Exo-GXM accumulates in patient serum and cerebrospinal fluid at microgram\/milliliter concentrations, has well-documented immunosuppressive properties, and correlates with poor patient outcomes. However, it is poorly understood whether exo-GXM release is regulated or the result of shedding during normal capsule turnover. We demonstrate that exo-GXM release is regulated by environmental cues and inversely correlates with surface capsule levels. We identified genes specifically involved in exo-GXM release that do not alter surface capsule thickness. The first mutant, the\n                    <jats:italic>liv7<\/jats:italic>\n                    \u0394 strain, released less GXM than wild-type cells when capsule was not induced. The second mutant, the\n                    <jats:italic>cnag_00658<\/jats:italic>\n                    \u0394 strain, released more exo-GXM under capsule-inducing conditions. Exo-GXM release observed\n                    <jats:italic>in vitro<\/jats:italic>\n                    correlated with polystyrene adherence, virulence, and fungal burden during murine infection. Additionally, we found that exo-GXM reduced cell size and capsule thickness under capsule-inducing conditions, potentially influencing dissemination. Finally, we demonstrated that exo-GXM prevents immune cell infiltration into the brain during disseminated infection and highly inflammatory intracranial infection. Our data suggest that exo-GXM performs a distinct role from capsule GXM during infection, altering cell size and suppressing inflammation.\n                  <\/jats:p>","DOI":"10.1128\/iai.00662-17","type":"journal-article","created":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T11:36:04Z","timestamp":1512387364000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Regulated Release of Cryptococcal Polysaccharide Drives Virulence and Suppresses Immune Cell Infiltration into the Central Nervous System"],"prefix":"10.1128","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3982-3835","authenticated-orcid":false,"given":"Steven T.","family":"Denham","sequence":"first","affiliation":[{"name":"Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-0267","authenticated-orcid":false,"given":"Surbhi","family":"Verma","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen L.","family":"Worne","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Daugherty","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Lane","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3255-1486","authenticated-orcid":false,"given":"Jessica C. S.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2015.6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.107.5.e66"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.10.3204-3209.1999"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1245"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01087-13"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30243-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052116"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07591"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198909213211205"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit435"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63734-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004754"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/655785"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.03.006"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-12"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.62.081307.162753"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323848"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01186.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.13.84"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.7.2846-2849.1996"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/426511"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6064-6073.2001"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.8.2919-2923.1995"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.2.664-669.1998"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1002476"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01125.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.9.4762-4771.2002"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.3.770-778.1995"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118466"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.1.59-64.1991"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir613"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw007"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0401.980109"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00378-07"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00437-07"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07511.x"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2015.11.010"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.5.2868-2875.2003"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2015.00101"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.12.7513"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02651.x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.046"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2007.10.012"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003168"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep21489"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.5027-5030.1998"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.MB-0006-2014"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.6350-6362.2005"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.141"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2016.04.008"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.10.012"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0036-46652015000700008"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12488"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000953"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000945"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03780.x"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00318-06"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.044"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.184101.114"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00273-13"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofv194"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.5.1053-1060.2003"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006340"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00354-4"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00662-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00662-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T05:58:48Z","timestamp":1646459928000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00662-17"}},"subtitle":[],"editor":[{"given":"George S.","family":"Deepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,3]]},"references-count":64,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1128\/IAI.00662-17"],"URL":"https:\/\/doi.org\/10.1128\/iai.00662-17","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/186668","asserted-by":"object"}]},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3]]},"assertion":[{"value":"2017-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00662-17"}}