{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:52:41Z","timestamp":1791352361568,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012699","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI177604"],"award-info":[{"award-number":["1R01AI177604"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["ZIA AI001175"],"award-info":[{"award-number":["ZIA AI001175"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Candida auris<\/jats:italic>\n                    is an emerging multidrug-resistant fungal pathogen that preferentially colonizes and persists in skin tissue, yet the host immune factors that regulate the skin colonization of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris in vivo<\/jats:italic>\n                    are unknown. In this study, we employed unbiased single-cell transcriptomics of murine skin infected with\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    to understand the cell type-specific immune response to\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    .\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    skin infection results in the accumulation of immune cells such as neutrophils, inflammatory monocytes, macrophages, dendritic cells, T cells, and NK cells at the site of infection. We identified fibroblasts as a major non-immune cell accumulated in the\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    infected skin tissue. The comprehensive single-cell profiling revealed the transcriptomic signatures in cytokines, chemokines, host receptors (TLRs, C-type lectin receptors, NOD receptors), antimicrobial peptides, and immune signaling pathways in individual immune and non-immune cells during\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    skin infection. Our analysis revealed that\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    infection upregulates the expression of the IL-1RN gene (encoding IL-1R antagonist protein) in different cell types. We found IL-1Ra produced by macrophages during\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    skin infection decreases the killing activity of neutrophils. Furthermore,\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    uses a unique cell wall mannan outer layer to evade IL-1R-signaling mediated host defense. Collectively, our single-cell RNA seq profiling identified the transcriptomic signatures in immune and non-immune cells during\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    skin infection. Our results demonstrate the IL-1Ra and IL-1R-mediated immune evasion mechanisms employed by\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    to persist in the skin. These results enhance our understanding of host defense and immune evasion mechanisms during\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>auris<\/jats:italic>\n                    skin infection and identify potential targets for novel antifungal therapeutics.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012699","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T13:35:17Z","timestamp":1731504917000},"page":"e1012699","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Single-cell transcriptomics unveils skin cell specific antifungal immune responses and IL-1Ra- IL-1R immune evasion strategies of emerging fungal pathogen Candida auris"],"prefix":"10.1371","volume":"20","author":[{"given":"Abishek","family":"Balakumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diprasom","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abtar","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett","family":"Bryak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrihari M.","family":"Ganesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail S.","family":"Lionakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devender","family":"Arora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothi","family":"Thimmapuram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0031-2392","authenticated-orcid":true,"given":"Shankar","family":"Thangamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"issue":"4","key":"ppat.1012699.ref001","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms9040807","article-title":"Candida auris: Epidemiology, Diagnosis, Pathogenesis, Antifungal Susceptibility, and Infection Control Measures to Combat the Spread of Infections in Healthcare Facilities.","volume":"9","author":"S Ahmad","year":"2021","journal-title":"Microorganisms."},{"key":"ppat.1012699.ref002","volume-title":"development and public health action","author":"WHO fungal priority pathogens list to guide research,","year":"2022"},{"issue":"7","key":"ppat.1012699.ref003","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1097\/CCM.0000000000004371","article-title":"Key Takeaways From the U.S. CDC\u2019s 2019 Antibiotic Resistance Threats Report for Frontline Providers.","volume":"48","author":"SS Kadri","year":"2020","journal-title":"Crit Care Med"},{"issue":"2","key":"ppat.1012699.ref004","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.chom.2020.12.002","article-title":"Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies","volume":"29","author":"X Huang","year":"2021","journal-title":"Cell Host 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Sparber","year":"2019","journal-title":"Cell Host Microbe."},{"issue":"8","key":"ppat.1012699.ref008","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1038\/s41591-021-01383-w","article-title":"Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility","volume":"27","author":"DM Proctor","year":"2021","journal-title":"Nature Medicine"},{"key":"ppat.1012699.ref009","doi-asserted-by":"crossref","first-page":"e0012724","DOI":"10.1128\/spectrum.00127-24","article-title":"Intradermal infection and dissemination of Candida auris in immunocompetent and immunocompromised mouse models.","author":"KA Towns","year":"2024","journal-title":"Microbiol Spectr."},{"issue":"5","key":"ppat.1012699.ref010","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/s41564-021-00875-2","article-title":"Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal 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