{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:12:16Z","timestamp":1778166736880,"version":"3.51.4"},"posted":{"date-parts":[[2024,10,22]]},"group-title":"Microbiology","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,10,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <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. 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. auris<\/jats:italic>\n                  to understand the cell type-specific immune response to\n                  <jats:italic>C. auris. C. 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. 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. auris<\/jats:italic>\n                  skin infection. Our analysis revealed that\n                  <jats:italic>C. 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. auris<\/jats:italic>\n                  skin infection decreases the killing activity of neutrophils. Furthermore,\n                  <jats:italic>C. 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. 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. 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. auris<\/jats:italic>\n                  skin infection and identify potential targets for novel antifungal therapeutics.\n                <\/jats:p>","DOI":"10.1101\/2024.10.22.619653","type":"posted-content","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T23:05:19Z","timestamp":1729638319000},"source":"Crossref","is-referenced-by-count":2,"title":["Single-Cell Transcriptomics Unveils Skin Cell Specific Antifungal Immune Responses and IL-1Ra-IL-1R Immune Evasion Strategies of Emerging Fungal Pathogen\n                  <i>Candida auris<\/i>"],"prefix":"10.64898","author":[{"given":"Abishek","family":"Balakumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diprasom","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhishek","family":"Datta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abtar","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett","family":"Bryak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shrihari M","family":"Ganesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michail S","family":"Lionakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devender","family":"Arora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyothi","family":"Thimmapuram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shankar","family":"Thangamani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024102514101614000_2024.10.22.619653v1.1","doi-asserted-by":"crossref","unstructured":"Ahmad, S. and W. 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