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The commensal pathobiont\n                  <jats:italic>Candida albicans<\/jats:italic>\n                  can cause severe oropharyngeal and mucocutaneous infections in immunocompromised individuals. The initial point of interaction of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  in the oral mucosa is with superficial oral epithelial cells (OECs). Upon fungal encounter, OECs upregulate a program of anti-fungal defense genes, a process that has been extensively studied at the level of proximal signaling pathways, transcriptional induction, and epigenetic control. However, inflammatory genes are also subject to extensive regulation at the mRNA level, yet little is known about mechanisms that control\n                  <jats:italic>C. albicans<\/jats:italic>\n                  -induced genes post-transcriptionally. The importance of \u2018epitranscriptomic\u2019 gene regulation by mRNA methylation is becoming increasingly appreciated, yet its contribution to host responses during fungal infection remains poorly understood. N6-methyladenosine (m\n                  <jats:sup>6<\/jats:sup>\n                  A) is the most abundant RNA modification and influences numerous transcript fates including mRNA stabilization. Here, we demonstrate that\n                  <jats:italic>C. albicans<\/jats:italic>\n                  -induced genes in human and mouse OECs are widely subject to m\n                  <jats:sup>6<\/jats:sup>\n                  A modification following infection. Silencing of a specific subclass of m\n                  <jats:sup>6<\/jats:sup>\n                  A binding proteins, the YTHDF1\/2\/3 \u2018readers\u2019, reprogrammed the OEC response to\n                  <jats:italic>C. albicans<\/jats:italic>\n                  by up- and down-regulating antifungal transcripts. The net effect of blocking the m\n                  <jats:sup>6<\/jats:sup>\n                  A pathway using a first-in-class METTL3 inhibitor was to amplify mRNA expression of antimicrobial peptides that reduce fungal burden. These studies establish a role for the m\n                  <jats:sup>6<\/jats:sup>\n                  A pathway as a modulator of immunity to mucosal candidiasis and suggest a new therapeutic avenue to treating this condition.\n                <\/jats:p>","DOI":"10.1101\/2025.09.07.674635","type":"posted-content","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T05:20:22Z","timestamp":1757308822000},"source":"Crossref","is-referenced-by-count":0,"title":["N6-methyladenosine (m\n                  <sup>6<\/sup>\n                  A) RNA modification restrains antifungal immunity and is a therapeutic target in oral candidiasis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2704-0451","authenticated-orcid":false,"given":"Nicole O.","family":"Ponde","sequence":"first","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2336-956X","authenticated-orcid":false,"given":"Melissa E.","family":"Cook","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ipsita","family":"Dey","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-3728","authenticated-orcid":false,"given":"Tiffany C.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca M.","family":"Coleman","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shachi P.","family":"Vyas","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1611-0242","authenticated-orcid":false,"given":"Rami","family":"Bechara","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, CEA; Immune Diseases, Microbiology and Innovative Therapies10 (IDMIT\/UMRS1184); Fontenay-aux-Roses & Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5747-064X","authenticated-orcid":false,"given":"Jishnu","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-2041","authenticated-orcid":false,"given":"Sarah L.","family":"Gaffen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081014000776000_2025.09.07.674635v2.1","first-page":"165rv13","article-title":"Hidden killers: Human fungal infections","volume":"4","year":"2012","journal-title":"Science Transl Med"},{"key":"2026081014000776000_2025.09.07.674635v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.05.013"},{"key":"2026081014000776000_2025.09.07.674635v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.10.001"},{"key":"2026081014000776000_2025.09.07.674635v2.4","doi-asserted-by":"crossref","unstructured":"Verma, A.H. et al. 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