{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T16:40:27Z","timestamp":1770914427996,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cutibacterium acnes, a major skin commensal bacterium, induces inflammatory cytokine production in keratinocytes through Toll-like receptor 2 (TLR2) signaling and contributes to acne vulgaris pathogenesis. Although glucocorticoids, e.g., dexamethasone (Dex), exert anti-inflammatory effects in related treatments, prolonged glucocorticoid exposure paradoxically induces acneiform eruptions, a phenomenon referred to as steroid-induced acne. Moreover, how commensal fungi influence bacterial-driven inflammatory signaling under glucocorticoid treatment remains unclear. In this study, we investigated how the lipophilic skin yeast Malassezia restricta affects C. acnes-induced TLR2 expression under Dex treatment using normal human epidermal keratinocytes. We discovered that M. restricta selectively suppressed Dex-enhanced C. acnes-induced TLR2 expression both at the transcriptional level and cell surface. Mechanistically, M. restricta enhanced p38 MAPK phosphorylation and inhibited NF-\u03baB p65 nuclear translocation, indicating context-dependent glucocorticoid-primed TLR2 signaling modulation rather than simple inhibition. These results demonstrate that M. restricta modulates bacterial-induced inflammatory responsiveness in keratinocytes under glucocorticoid exposure and highlight the importance of fungal\u2013bacterial interactions in shaping host immune signaling in steroid-treated skin. Our study provides new insight into the mechanistic basis of steroid-induced acne and the polymicrobial regulation of cutaneous innate immunity.<\/jats:p>","DOI":"10.3390\/microorganisms14020450","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:28:11Z","timestamp":1770910091000},"page":"450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fungal\u2013Bacterial Crosstalk Modulates Glucocorticoid-Primed TLR2 Signaling in the Human Skin"],"prefix":"10.3390","volume":"14","author":[{"given":"Otomi","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Microbiology, Meiji Pharmaceutical University, Tokyo 204-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanako","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Meiji Pharmaceutical University, Tokyo 204-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Sugita","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Meiji Pharmaceutical University, Tokyo 204-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrmicro.2017.157","article-title":"The human skin microbiome","volume":"16","author":"Byrd","year":"2018","journal-title":"Nat. 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