{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:08Z","timestamp":1787018348797,"version":"build-2736575974"},"reference-count":101,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["DE022550"],"award-info":[{"award-number":["DE022550"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI110820"],"award-info":[{"award-number":["AI110820"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK120697"],"award-info":[{"award-number":["DK120697"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,22]]},"abstract":"<jats:p>\n                    A side effect of antibiotics is outgrowth of the opportunistic fungus\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    in the oropharynx (oropharyngeal candidiasis, OPC). IL-17 signaling is vital for immunity to OPC, but how the microbiome impacts antifungal immunity is not well understood. Mice in standard specific pathogen\u2013free (SPF) conditions are resistant to OPC, whereas we show that germ-free (GF) or antibiotic-treated mice are susceptible. Oral type 17 cells and IL-17\u2013dependent responses were impaired in antibiotic-treated and GF mice. Susceptibility could be rescued in GF mice by mono-colonization with segmented filamentous bacterium (SFB), an intestine-specific constituent of the microbiota. SFB protection was accompanied by restoration of oral IL-17\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and gene signatures characteristic of IL-17 signaling. Additionally, RNA-Seq revealed induction of genes in the retinoic acid (RA) and RA receptor\u2013\u03b1 (RAR\u03b1) pathway. Administration of RA rescued immunity to OPC in microbiome-depleted or GF mice, while RAR inhibition caused susceptibility in immunocompetent animals. Surprisingly, immunity to OPC was independent of serum amyloids. Moreover, RAR inhibition did not alter oral type 17 cytokine levels. Thus, mono-colonization with a component of the intestinal microflora confers protection against OPC by type 17 and RA\/RAR\u03b1, which act in parallel to promote antifungal immunity. In principle, manipulation of the microbiome could be harnessed to maintain antifungal immunity.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.160348","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T14:00:48Z","timestamp":1663768848000},"source":"Crossref","is-referenced-by-count":22,"title":["A gut-oral microbiome\u2013driven axis controls oropharyngeal candidiasis through retinoic acid"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0327-0095","authenticated-orcid":true,"given":"Felix E.Y.","family":"Aggor","sequence":"first","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martinna","family":"Bertolini","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, and"},{"name":"Department of Periodontics and Preventive Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9721-7948","authenticated-orcid":true,"given":"Chunsheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-3728","authenticated-orcid":true,"given":"Tiffany C.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl A.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Richard King Mellon Foundation Institute for Pediatric Research, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javonn","family":"Musgrove","sequence":"additional","affiliation":[{"name":"Richard King Mellon Foundation Institute for Pediatric Research, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Hand","sequence":"additional","affiliation":[{"name":"Richard King Mellon Foundation Institute for Pediatric Research, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-2041","authenticated-orcid":true,"given":"Sarah L.","family":"Gaffen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034511399284"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053318"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mmcr.2012.02.003"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.03.006"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000031"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/foac019"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S118892"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081463"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500909"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200439"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.10.016"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01389-13"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.09.002"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747209"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aba0570"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.97"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nri3493"},{"issue":"165","key":"B18","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: human fungal infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci Transl Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007460"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nature18848"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.08.007"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.01.016"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.02.004"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1205177"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/jof6010015"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00426"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aau4594"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.12.010"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12378"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.048"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12950"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.061"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01214-7"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01403"},{"issue":"3\u20134","key":"B35","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1574-6968.1992.tb04986.x","article-title":"Intestinal, segmented, filamentous bacteria","volume":"8","author":"Klaasen","year":"1992","journal-title":"FEMS Microbiol Rev"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502566"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.007"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.03.004"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.09.010"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.09.028"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf9232"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.011"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.10.001"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200594"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1906s105"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.128"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s40588-018-0098-6"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4A0915-428R"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.033"},{"issue":"4","key":"B50","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41374-021-00697-0","article-title":"Commensal gut bacterium critically regulates alveolar bone homeostasis","volume":"102","author":"Hathaway-Schrader","year":"2021","journal-title":"Lab Invest"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/jof3040060"},{"issue":"17","key":"B52","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aam8834","article-title":"Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin","volume":"2","author":"Verma","year":"2017","journal-title":"Sci Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130877"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007069"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12036"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5731"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/nature13279"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1186\/1480-9222-16-4"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.026"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2021.07.011"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00201-15"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121588"},{"key":"B63","article-title":"Retinoic acid mediated clearance of Citrobacter rodentium in vitamin A deficient mice requires CD11b+ and T cells","volume":"9","author":"Snyder","year":"2018","journal-title":"Front Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-014-0351-4"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/ph14100962"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1177\/10454411000110040101"},{"issue":"15","key":"B67","doi-asserted-by":"crossref","DOI":"10.1242\/dev.164822","article-title":"RDH10-mediated retinol metabolism and RAR\u03b1-mediated retinoic acid signaling are required for submandibular salivary gland initiation","volume":"145","author":"Metzler","year":"2018","journal-title":"Development"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.04.013"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1126\/science.1221789"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/s40588-018-0096-8"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.07.025"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.05.002"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.2"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aba4163"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.041"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.01.017"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.02.009"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.09.009"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.10.007"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1398-6"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.03.013"},{"issue":"4","key":"B82","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.140738","article-title":"Commensal oral microbiota induces osteoimmunomodulatory effects separate from systemic microbiome in mice","volume":"7","author":"Hathaway-Schrader","year":"2022","journal-title":"JCI Insight"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7090258"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-071219-125715"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01995"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903942"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2286"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.003"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1783"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202924"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01247-6"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01252-9"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.002"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110308"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1812069116"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.029579"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe6723"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2006.00450.x"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.11.021"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00469-16"},{"issue":"9","key":"B101","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1093\/infdis\/jiz649","article-title":"The interleukin (IL) 17R\/IL-22R signaling axis is dispensable for vulvovaginal Candidiasis regardless of estrogen status","volume":"221","author":"Peters","year":"2019","journal-title":"J Infect Dis"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/160348\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:29:30Z","timestamp":1779146970000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/160348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":101,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9,22]]},"published-print":{"date-parts":[[2022,9,22]]}},"alternative-id":["10.1172\/jci.insight.160348"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.160348","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,22]]},"article-number":"e160348"}}