{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T10:35:03Z","timestamp":1773398103140,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica-FONCyT","doi-asserted-by":"crossref","award":["PICT-2019\u20132012"],"award-info":[{"award-number":["PICT-2019\u20132012"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica-FONCyT","doi-asserted-by":"crossref","award":["PICT-2021-00333"],"award-info":[{"award-number":["PICT-2021-00333"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SECyT-UNC","award":["30720150100934CB"],"award-info":[{"award-number":["30720150100934CB"]}]},{"name":"SECyT-UNC","award":["33620230100340CB"],"award-info":[{"award-number":["33620230100340CB"]}]},{"DOI":"10.13039\/501100002923","name":"CONICET","doi-asserted-by":"crossref","award":["11220220100579CO"],"award-info":[{"award-number":["11220220100579CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]},{"name":"AltaMed Health Service Corporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Candida albicans is the primary agent of acute vulvovaginal candidiasis (VVC) and its recurrent form (RVVC). Local innate immunity contributes to both defense and pathogenesis during vaginal Candida infection, where epithelial \u03b2-defensins (BD) constitute key components of the mucosal barrier. We previously reported that epithelial BD-1 expression is dynamically modulated during murine and human vaginitis, revealing strain-dependent and stimulus-specific regulation but leaving the host pathways involved unresolved. This study functionally defines the contribution of key immune pathways to epithelial antimicrobial peptide regulation. Using a murine model of VVC and the virulent C. albicans strain SC5314, we aimed to evaluate the immune signaling pathways governing the temporal regulation of epithelial BD-1 and BD-3 expression during vaginal infection. In wild-type mice, both defensins displayed a biphasic pattern: early induction followed by attenuation as infection progressed. Genetic loss-of-function approaches revealed that NLRP3\/IL-1\u03b2 signaling is required for early BD-1 induction, whereas IL-17RA signaling preferentially supports sustained BD-3 expression. Together, these findings establish a causal and temporal link between host immune signaling and epithelial defensin regulation and reveal a transient subversion of mucosal defenses by C. albicans. This work advances understanding of epithelial innate immunity, defining distinct temporal programs for BD-1 and BD-3 and identifying NLRP3\/IL-1\u03b2 and IL-17RA signaling as key pathways shaping mucosal defensin expression.<\/jats:p>","DOI":"10.3390\/jof12030204","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T09:00:37Z","timestamp":1773219637000},"page":"204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biphasic Regulation of Epithelial Antimicrobial Peptides During Candida albicans Vaginal Infection: Distinct Contributions of NLRP3\/IL-1\u03b2 and IL-17RA Pathways to \u03b2-Defensin-1 and -3 Expression"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9242-975X","authenticated-orcid":false,"given":"Sof\u00eda Carla","family":"Angiolini","sequence":"first","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"},{"name":"Center for Research in Clinical Biochemistry and Immunology, CIBICI-CONICET, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"},{"name":"Research Group of Immunology and Mycology, C\u00f3rdoba 5000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4100-8506","authenticated-orcid":false,"given":"Emilse","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"},{"name":"Center for Research in Clinical Biochemistry and Immunology, CIBICI-CONICET, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"},{"name":"Research Group of Immunology and Mycology, C\u00f3rdoba 5000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarisa","family":"Manzone-Rodriguez","sequence":"additional","affiliation":[{"name":"Center for Research in Clinical Biochemistry and Immunology, CIBICI-CONICET, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0457-7523","authenticated-orcid":false,"given":"Paula Alejandra","family":"Icely","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"},{"name":"Center for Research in Clinical Biochemistry and Immunology, CIBICI-CONICET, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"},{"name":"Research Group of Immunology and Mycology, C\u00f3rdoba 5000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6671-5053","authenticated-orcid":false,"given":"Mar\u00eda Soledad","family":"Mir\u00f3","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"},{"name":"Center for Research in Clinical Biochemistry and Immunology, CIBICI-CONICET, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"},{"name":"Research Group of Immunology and Mycology, C\u00f3rdoba 5000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0618-1899","authenticated-orcid":false,"given":"Fernando Oscar","family":"Riera","sequence":"additional","affiliation":[{"name":"Research Group of Immunology and Mycology, C\u00f3rdoba 5000, Argentina"},{"name":"Division of Infectious Diseases, Sanatorio Allende, C\u00f3rdoba 5000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5679-4386","authenticated-orcid":false,"given":"Pablo","family":"Iribarren","sequence":"additional","affiliation":[{"name":"Center for Research in Clinical Biochemistry and Immunology, CIBICI-CONICET, National University of C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6172-1395","authenticated-orcid":false,"given":"Juan Pablo","family":"Caeiro","sequence":"additional","affiliation":[{"name":"Research Group of Immunology and Mycology, C\u00f3rdoba 5000, Argentina"},{"name":"Division of Infectious Diseases, AltaMed Health Service Corporation, Los Angeles, CA 90040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2449-0852","authenticated-orcid":false,"given":"Claudia 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