{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:25:47Z","timestamp":1791959147980,"version":"4.3.4"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"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":[[2025,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Cryptococcus neoformans<\/jats:italic>\n              is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Both host- and pathogen-specific factors are known to affect patient outcome, and recent studies showed that strain-specific differences in\n              <jats:italic>C. neoformans<\/jats:italic>\n              clinical isolates can influence virulence in A\/J mice. However, it is unclear how the immunologic and genetic background of inbred mouse strains affects disease outcome during\n              <jats:italic>C. neoformans<\/jats:italic>\n              infection. In this study, we show that a hypervirulent phenotype is dependent on the host immune response and mouse genetic background. A\/J mice intranasally infected with the hypervirulent isolates, UgCl247, UgCl422, and UgCl236, have increased neutrophil and T-cell recruitment when compared with infection with the reference strain KN99\u03b1. In addition, the cytokine profile of the hypervirulent isolates in A\/J mice had a profound IFN\u03b3 and IL-17 response, and lung resident CD4 T-cells isolated from A\/J mice expressed significantly increased Th1 (CXCR3, Tbet) and Th17 (ROR\u03b3T) markers compared with KN99\u03b1 infection. Intriguingly, when C57BL\/6J mice were infected with these isolates, the hypervirulent phenotype was not evident, and all isolates had virulence comparable to the KN99\u03b1 control. The immune response in C57BL\/6J mice was also nearly identical in response to infections with the hypervirulent isolates and the KN99\u03b1 control strain. Finally, we determined that the hypervirulent phenotype in A\/J mice is not caused by known genetic mutations in the A\/J inbred mouse background. Overall, this study demonstrates that an inbred mouse inhalation model can be used to identify host- and pathogen-specific factors that affect\n              <jats:italic>C. neoformans<\/jats:italic>\n              disease progression.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00585-24","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T15:30:02Z","timestamp":1741015802000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["The hypervirulent Type-1\/Type-17 phenotype of\n            <i>Cryptococcus neoformans<\/i>\n            clinical isolates is specific to A\/J mice"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-8157","authenticated-orcid":true,"given":"Minna","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2944-8015","authenticated-orcid":false,"given":"Katrina M.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota","place":["Minneapolis, USA"]},{"name":"Pathogen and Microbiome Institute, Northern Arizona University","place":["Flagstaff, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Harris-Gordon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamotharampillai","family":"Dileepan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Meya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2318-168X","authenticated-orcid":true,"given":"Kirsten","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota","place":["Minneapolis, USA"]},{"name":"Department of Biomedical Sciences and Pathology, Virginia Tech","place":["Blacksburg, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00499-6"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix033"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof3020028"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209337"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000001382"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv067"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofv194"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004701"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003847"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0193237"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005223"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0267842"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02626-22"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01440-19"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00046-19"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myaa013"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54729-6"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/08830180213274"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01270-10"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760180060"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1177\/0300985811429314"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.055"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2010.158"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof3040064"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.6.2959-2964.2002"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2014.09.004"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02016-18"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00196-12"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2018.1562849"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12281-011-0064-8"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00094-07"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.160.5.2393"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.29.2.494-499.1980"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof10060426"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00350-08"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02063-17"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20191736"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312884"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.9.4831-4841.2003"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.105.045039"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.005"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150606"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.007"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00585-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00585-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T13:08:59Z","timestamp":1744117739000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00585-24"}},"subtitle":[],"editor":[{"given":"Andreas J.","family":"B\u00e4umler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,8]]}},"alternative-id":["10.1128\/iai.00585-24"],"URL":"https:\/\/doi.org\/10.1128\/iai.00585-24","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,8]]},"assertion":[{"value":"2024-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00585-24"}}