{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:31:29Z","timestamp":1791923489240,"version":"4.3.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["RP-2017\u201308-ST2-012"],"award-info":[{"award-number":["RP-2017\u201308-ST2-012"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Strategic Award for Medical Mycology and Fungal Immunology","award":["097377\/Z\/11\/Z"],"award-info":[{"award-number":["097377\/Z\/11\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans are opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of human immunodeficiency virus\u2013related deaths globally, with the majority occurring in Africa. The human immune response to C albicans infection has been studied extensively in large genomics studies whereas cryptococcal infections, despite their severity, are comparatively understudied. Here we investigated the transcriptional response of immune cells after in vitro stimulation with in vitro C neoformans, C gattii, and C albicans infection of peripheral blood mononuclear cells collected from healthy South African volunteers. We found a lower transcriptional response to cryptococcal stimuli compared to C albicans and unique expression signatures from all 3 fungal stimuli. This work provides a starting point for further studies comparing the transcriptional signature of CM in immunocompromised patients, with the goal of identifying biomarkers of disease severity and possible novel treatment targets.<\/jats:p>","DOI":"10.1093\/infdis\/jiae410","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T13:41:49Z","timestamp":1724074909000},"page":"e254-e262","source":"Crossref","is-referenced-by-count":2,"title":["Ex Vivo Host Transcriptomics During <i>Cryptococcus neoformans<\/i>, <i>Cryptococcus gattii<\/i>, and <i>Candida albicans<\/i> Infection of Peripheral Blood Mononuclear Cells From South African Volunteers"],"prefix":"10.1093","volume":"231","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5001-1945","authenticated-orcid":false,"given":"Ronan M","family":"Doyle","sequence":"first","affiliation":[{"name":"Department of Clinical Research, London School of Hygiene and Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichina","family":"Kannambath","sequence":"additional","affiliation":[{"name":"Genomics Facility, The Institute of Cancer Research"},{"name":"Institute of Infection and Immunity, St George's University London, and Clinical Academic Group in Infection, St George's University Hospitals NHS Foundation Trust , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Pittman","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, St George's University London, and Clinical Academic Group in Infection, St George's University Hospitals NHS Foundation Trust , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Goliath","sequence":"additional","affiliation":[{"name":"Department of Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[{"name":"Botswana Harvard Health Partnership , Gaborone"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Meintjes","sequence":"additional","affiliation":[{"name":"Department of Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9885-6103","authenticated-orcid":false,"given":"James","family":"Milburn","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, London School of Hygiene and Tropical Medicine"},{"name":"Botswana Harvard Health Partnership , Gaborone"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S","family":"Harrison","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, St George's University London, and Clinical Academic Group in Infection, St George's University Hospitals NHS Foundation Trust , London ,","place":["United Kingdom"]},{"name":"Medical Research Council Centre for Medical Mycology, University of Exeter ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph N","family":"Jarvis","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, London School of Hygiene and Tropical Medicine"},{"name":"Botswana Harvard Health Partnership , Gaborone"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2676-838X","authenticated-orcid":false,"given":"Tihana","family":"Bicanic","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, St George's University London, and Clinical Academic Group in Infection, St George's University Hospitals NHS Foundation Trust , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"2025020417132486200_jiae410-B1","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/S1473-3099(22)00499-6","article-title":"The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis","volume":"22","author":"Rajasingham","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"2025020417132486200_jiae410-B2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/mmy.38.6.407.417","article-title":"Immunoregulation by capsular components of Cryptococcus neoformans","volume":"38","author":"Vecchiarelli","year":"2000","journal-title":"Med Mycol"},{"key":"2025020417132486200_jiae410-B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13693780500088424","article-title":"Role of CD4+ T cells in a protective immune response against Cryptococcus neoformans in the central nervous system","volume":"44","author":"Uicker","year":"2006","journal-title":"Med Mycol"},{"key":"2025020417132486200_jiae410-B4","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1093\/infdis\/jit099","article-title":"The phenotype of the Cryptococcus-specific CD4+ memory T-cell response is associated with disease severity and outcome in HIV-associated cryptococcal meningitis","volume":"207","author":"Jarvis","year":"2013","journal-title":"J Infect Dis"},{"key":"2025020417132486200_jiae410-B5","doi-asserted-by":"crossref","first-page":"e1004754","DOI":"10.1371\/journal.ppat.1004754","article-title":"Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis","volume":"11","author":"Jarvis","year":"2015","journal-title":"PLoS Pathog"},{"key":"2025020417132486200_jiae410-B6","doi-asserted-by":"crossref","first-page":"e1006207","DOI":"10.1371\/journal.ppat.1006207","article-title":"Immune correlates of HIV-associated cryptococcal meningitis","volume":"13","author":"Tenforde","year":"2017","journal-title":"PLoS Pathog"},{"key":"2025020417132486200_jiae410-B7","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.4049\/jimmunol.129.4.1675","article-title":"The capsule of Cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages","volume":"129","author":"Kozel","year":"1982","journal-title":"J Immunol"},{"key":"2025020417132486200_jiae410-B8","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1128\/IAI.67.2.885-890.1999","article-title":"Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages","volume":"67","author":"Levitz","year":"1999","journal-title":"Infect Immun"},{"key":"2025020417132486200_jiae410-B9","doi-asserted-by":"crossref","first-page":"e15968","DOI":"10.1371\/journal.pone.0015968","article-title":"Automated analysis of cryptococcal macrophage parasitism using GFP-tagged cryptococci","volume":"5","author":"Voelz","year":"2010","journal-title":"PLoS One"},{"key":"2025020417132486200_jiae410-B10","doi-asserted-by":"crossref","first-page":"ofaa489","DOI":"10.1093\/ofid\/ofaa489","article-title":"Genome-wide association study identifies novel colony stimulating factor 1 locus conferring susceptibility to cryptococcosis in human immunodeficiency virus\u2013infected South Africans","volume":"7","author":"Kannambath","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"2025020417132486200_jiae410-B11","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1038\/ncomms2343","article-title":"Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans","volume":"4","author":"Smeekens","year":"2013","journal-title":"Nat Commun"},{"key":"2025020417132486200_jiae410-B12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.chom.2012.06.006","article-title":"Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes","volume":"12","author":"Quintin","year":"2012","journal-title":"Cell Host Microbe"},{"key":"2025020417132486200_jiae410-B13","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1128\/EC.3.5.1076-1087.2004","article-title":"Transcriptional response of Candida albicans upon internalization by macrophages","volume":"3","author":"Lorenz","year":"2004","journal-title":"Eukaryot Cell"},{"key":"2025020417132486200_jiae410-B14","doi-asserted-by":"crossref","first-page":"6445","DOI":"10.1128\/IAI.69.10.6445-6455.2001","article-title":"Both Th1 and Th2 cytokines affect the ability of monoclonal antibodies to protect mice against Cryptococcus neoformans","volume":"69","author":"Beenhouwer","year":"2001","journal-title":"Infect Immun"},{"key":"2025020417132486200_jiae410-B15","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.4049\/jimmunol.174.3.1746","article-title":"IFN-gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis","volume":"174","author":"Siddiqui","year":"2005","journal-title":"J Immunol"},{"key":"2025020417132486200_jiae410-B16","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/infdis\/jiw007","article-title":"A glucuronoxylomannan-associated immune signature, characterized by monocyte deactivation and an increased interleukin 10 level, is a predictor of death in cryptococcal meningitis","volume":"213","author":"Scriven","year":"2016","journal-title":"J Infect Dis"},{"key":"2025020417132486200_jiae410-B17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2025020417132486200_jiae410-B18","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2025020417132486200_jiae410-B19","doi-asserted-by":"crossref","first-page":"R14","DOI":"10.1186\/gb-2010-11-2-r14","article-title":"Gene ontology analysis for RNA-seq: accounting for selection bias","volume":"11","author":"Young","year":"2010","journal-title":"Genome Biol"},{"key":"2025020417132486200_jiae410-B20","doi-asserted-by":"crossref","first-page":"D687","DOI":"10.1093\/nar\/gkab1028","article-title":"The Reactome pathway knowledge base 2022","volume":"50","author":"Gillespie","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2025020417132486200_jiae410-B21","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1056\/NEJMra1315399","article-title":"Invasive candidiasis","volume":"373","author":"Kullberg","year":"2015","journal-title":"N Engl J Med"},{"key":"2025020417132486200_jiae410-B22","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1086\/649858","article-title":"Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America","volume":"50","author":"Perfect","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2025020417132486200_jiae410-B23","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.fgb.2014.11.006","article-title":"Immunity to Cryptococcus neoformans and C. gattii during cryptococcosis","volume":"78","author":"Gibson","year":"2015","journal-title":"Fungal Genet Biol"},{"key":"2025020417132486200_jiae410-B24","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1159\/000430375","article-title":"Cryptococcus neoformans infection and immune cell regulation in human monocytes","volume":"37","author":"Chen","year":"2015","journal-title":"Cell Physiol Biochem"},{"key":"2025020417132486200_jiae410-B25","doi-asserted-by":"crossref","first-page":"e165","DOI":"10.1016\/j.jinf.2006.10.002","article-title":"Immune dysfunction in HIV-seronegative, Cryptococcus gattii meningitis","volume":"54","author":"Brouwer","year":"2007","journal-title":"J Infect"},{"key":"2025020417132486200_jiae410-B26","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1002\/eji.201343828","article-title":"Differential role of NK cells against Candida albicans infection in immunocompetent or immunocompromised mice","volume":"44","author":"Quintin","year":"2014","journal-title":"Eur J Immunol"},{"key":"2025020417132486200_jiae410-B27","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3390\/jof8050430","article-title":"Transcriptional profiles elucidate differential host responses to infection with Cryptococcus neoformans and Cryptococcus gattii","volume":"8","author":"Holcomb","year":"2022","journal-title":"J Fungi"},{"key":"2025020417132486200_jiae410-B28","doi-asserted-by":"crossref","first-page":"ofy157","DOI":"10.1093\/ofid\/ofy157","article-title":"Transcriptomic predictors of paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome","volume":"5","author":"Vlasova-St Louis","year":"2018","journal-title":"Open Forum Infect Dis"},{"key":"2025020417132486200_jiae410-B29","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1093\/infdis\/jir458","article-title":"Genetic variation in the Dectin-1\/CARD9 recognition pathway and susceptibility to candidemia","volume":"204","author":"Rosentul","year":"2011","journal-title":"J Infect Dis"},{"key":"2025020417132486200_jiae410-B30","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1089\/jir.2015.0040","article-title":"The role of Dectin-2 for host defense against disseminated candidiasis","volume":"36","author":"Ifrim","year":"2016","journal-title":"J Interferon Cytokine Res"},{"key":"2025020417132486200_jiae410-B31","doi-asserted-by":"crossref","first-page":"e0220989","DOI":"10.1371\/journal.pone.0220989","article-title":"Cryptococcus gattii alters immunostimulatory potential in response to the environment","volume":"14","author":"Ueno","year":"2019","journal-title":"PLoS One"},{"key":"2025020417132486200_jiae410-B32","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1086\/597274","article-title":"Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1\u03b2 production by the fungal pathogen Candida albicans","volume":"199","author":"van de Veerdonk","year":"2009","journal-title":"J Infect Dis"},{"key":"2025020417132486200_jiae410-B33","doi-asserted-by":"crossref","first-page":"e1008408","DOI":"10.1371\/journal.ppat.1008408","article-title":"Integrating GWAS with bulk and single-cell RNA-sequencing reveals a role for LY86 in the anti-Candida host response","volume":"16","author":"de Vries","year":"2020","journal-title":"PLoS Pathog"},{"key":"2025020417132486200_jiae410-B34","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1080\/13693780600750022","article-title":"Heat killed cells of Cryptococcus neoformans var. grubii induces protective immunity in rats: immunological and histopathological parameters","volume":"44","author":"Baronetti","year":"2006","journal-title":"Med Mycol"},{"key":"2025020417132486200_jiae410-B35","doi-asserted-by":"crossref","first-page":"e55579","DOI":"10.1371\/journal.pone.0055579","article-title":"Cryptococcus gattii induces a cytokine pattern that is distinct from other cryptococcal species","volume":"8","author":"Schoffelen","year":"2013","journal-title":"PLoS One"},{"key":"2025020417132486200_jiae410-B36","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1172\/JCI72950","article-title":"Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis","volume":"124","author":"Sabiiti","year":"2014","journal-title":"J Clin Invest"},{"key":"2025020417132486200_jiae410-B37","doi-asserted-by":"crossref","first-page":"e0233818","DOI":"10.1371\/journal.pone.0233818","article-title":"Intracellular Cryptococcus neoformans disrupts the transcriptome profile of M1- and M2-polarized host macrophages","volume":"15","author":"Subramani","year":"2020","journal-title":"PLoS One"},{"key":"2025020417132486200_jiae410-B38","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1128\/IAI.67.5.2218-2224.1999","article-title":"Antibody response to Cryptococcus neoformans proteins in rodents and humans","volume":"67","author":"Chen","year":"1999","journal-title":"Infect Immun"},{"key":"2025020417132486200_jiae410-B39","doi-asserted-by":"crossref","first-page":"E66","DOI":"10.1542\/peds.107.5.e66","article-title":"Serologic evidence for Cryptococcus neoformans infection in early childhood","volume":"107","author":"Goldman","year":"2001","journal-title":"Pediatrics"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiae410\/58935553\/jiae410.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/231\/1\/e254\/58935553\/jiae410.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/231\/1\/e254\/58935553\/jiae410.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T17:19:25Z","timestamp":1738689565000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/231\/1\/e254\/7735862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,19]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,8,19]]},"published-print":{"date-parts":[[2025,2,4]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiae410","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1,15]]},"published":{"date-parts":[[2024,8,19]]}}}