{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:22:25Z","timestamp":1789431745324,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014202","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000}}],"reference-count":113,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21-AI185365"],"award-info":[{"award-number":["R21-AI185365"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32-AI089443"],"award-info":[{"award-number":["T32-AI089443"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F32-AI186291"],"award-info":[{"award-number":["F32-AI186291"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI134796"],"award-info":[{"award-number":["R01-AI134796"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Vulvovaginal candidiasis (VVC) affects &gt;75% of women, with considerable morbidity and high medical cost burden. While Type 17 cytokines (IL-17, IL-22) are critical for oral and dermal immunity to\n                    <jats:italic>C. albicans<\/jats:italic>\n                    , their role in VVC has been less clear. Th17 gene signatures are potently upregulated in VVC, yet impairment of individual Th17 components (IL-17A, IL-17R subunits, IL-22) does not worsen disease. Rather, estrogen activity is tightly linked to VVC, leading to a paradigm that hormonal pathways, rather than immune defense, dominate susceptibility. Here, we reveal a previously unappreciated role for IL-1\/Type 17 in VVC that operates independently of estrogenic hormones. In contrast to mice lacking IL-17A, IL-17RA, IL-22, or IL-22R individually, mice lacking IL-17RA and IL-22RA1 together (\n                    <jats:italic>Il17raIl22ra1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    ) exhibited high fungal loads and exacerbated tissue damage and inflammation during estrogen-induced VVC. In human vulvar epithelial cells, IL-17 and IL-22 drive synergistic signaling. IL-1R signaling but surprisingly not IL-23 was upstream of this response.\n                    <jats:italic>Il17raIl22ra1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice expressed high IL-1\u03b2 yet did not control disease, indicating that IL-1 is upstream but not downstream of Type 17 responses. Unexpectedly, Type 17-dependent control occurred in the absence of exogenous estrogen administration and persisted even when estrus was prevented by progesterone treatment. Collectively, these data indicate that susceptibility to VVC is driven not only by estrogen sensitization but through combinatorial loss of IL-17 and IL-22.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014202","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T17:42:15Z","timestamp":1778175735000},"page":"e1014202","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["An IL-1, IL-17, and IL-22 cytokine circuit controls vulvovaginal candidiasis independently of estrogen"],"prefix":"10.1371","volume":"22","author":[{"given":"Bianca M.","family":"Coleman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Robin","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda K.","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shachi P.","family":"Vyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany C.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix E.Y.","family":"Aggor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole O.","family":"Ponde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ipsita","family":"Dey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eldin","family":"Ja\u0161arevi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-2041","authenticated-orcid":true,"given":"Sarah L.","family":"Gaffen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"issue":"7","key":"ppat.1014202.ref001","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S2666-5247(24)00042-9","article-title":"The WHO fungal priority pathogens list: A crucial reappraisal to review the prioritisation","volume":"5","author":"G Casalini","year":"2024","journal-title":"Lancet Microbe"},{"key":"ppat.1014202.ref002","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev-immunol-042617-053318","article-title":"Host control of fungal infections: Lessons from basic studies and human cohorts","volume":"36","author":"MS Lionakis","year":"2018","journal-title":"Annu Rev Immunol"},{"issue":"43","key":"ppat.1014202.ref003","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aau4594","article-title":"Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity","volume":"5","author":"SL Gaffen","year":"2020","journal-title":"Sci Immunol"},{"issue":"1","key":"ppat.1014202.ref004","article-title":"Vulvovaginal candidiasis: A current understanding and burning questions","volume":"6","author":"HME Willems","year":"2020","journal-title":"J Fungi (Basel)"},{"issue":"2","key":"ppat.1014202.ref005","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00645-17","article-title":"Candidalysin drives epithelial signaling, neutrophil recruitment, and immunopathology at the vaginal mucosa","volume":"86","author":"JP Richardson","year":"2018","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1014202.ref006","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.cyto.2011.11.021","article-title":"Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins","volume":"58","author":"J Yano","year":"2012","journal-title":"Cytokine"},{"issue":"10","key":"ppat.1014202.ref007","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/j.chom.2024.08.018","article-title":"Host-microbe interaction paradigms in acute and recurrent vulvovaginal candidiasis","volume":"32","author":"J MacAlpine","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ppat.1014202.ref008","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/978-0-387-09550-9_11","article-title":"The damage-response framework of microbial pathogenesis and infectious diseases","volume":"635","author":"L Pirofski","year":"2008","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"ppat.1014202.ref009","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/IAI.02627-14","article-title":"What is a host? Incorporating the microbiota into the damage-response framework","volume":"83","author":"A Casadevall","year":"2015","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1014202.ref010","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3390\/jof6010035","article-title":"Applying the host-microbe damage response framework to candida pathogenesis: Current and prospective strategies to reduce damage","volume":"6","author":"PL Fidel","year":"2020","journal-title":"J Fungi (Basel)"},{"issue":"5","key":"ppat.1014202.ref011","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.tim.2004.03.006","article-title":"History and new insights into host defense against vaginal candidiasis","volume":"12","author":"PL Fidel","year":"2004","journal-title":"Trends Microbiol"},{"issue":"3","key":"ppat.1014202.ref012","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1128\/IAI.66.3.1273-1275.1998","article-title":"Acute neutropenia decreases inflammation associated with murine vaginal candidiasis but has no effect on the course of infection","volume":"66","author":"CA Black","year":"1998","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1014202.ref013","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1128\/IAI.68.2.651-657.2000","article-title":"Effects of reproductive hormones on experimental vaginal candidiasis","volume":"68","author":"PL Fidel","year":"2000","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1014202.ref014","doi-asserted-by":"crossref","first-page":"11247","DOI":"10.1038\/s41598-018-29423-5","article-title":"Estrogen action in the epithelial cells of the mouse vagina regulates neutrophil infiltration and vaginal tissue integrity","volume":"8","author":"S Li","year":"2018","journal-title":"Sci Rep"},{"key":"ppat.1014202.ref015","article-title":"Protocols for vaginal inoculation and sample collection in the experimental mouse model of Candida vaginitis","volume":"58","author":"J Yano","year":"2011","journal-title":"J Vis Exp"},{"issue":"47","key":"ppat.1014202.ref016","doi-asserted-by":"crossref","first-page":"5549","DOI":"10.1016\/j.vaccine.2013.09.016","article-title":"NDV-3 protects mice from vulvovaginal candidiasis through T- and B-cell immune response","volume":"31","author":"AS Ibrahim","year":"2013","journal-title":"Vaccine"},{"issue":"12","key":"ppat.1014202.ref017","article-title":"Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice","volume":"5","author":"L Lin","year":"2009","journal-title":"PLoS Pathog"},{"issue":"52","key":"ppat.1014202.ref018","doi-asserted-by":"crossref","first-page":"7594","DOI":"10.1016\/j.vaccine.2012.10.038","article-title":"NDV-3, a recombinant alum-adjuvanted vaccine for Candida and Staphylococcus aureus, is safe and immunogenic in healthy adults","volume":"30","author":"CS Schmidt","year":"2012","journal-title":"Vaccine"},{"key":"ppat.1014202.ref019","doi-asserted-by":"crossref","first-page":"925821","DOI":"10.3389\/fimmu.2022.925821","article-title":"Antibodies targeting Candida albicans Als3 and Hyr1 antigens protect neonatal mice from candidiasis","volume":"13","author":"S Singh","year":"2022","journal-title":"Front Immunol"},{"issue":"12","key":"ppat.1014202.ref020","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1093\/cid\/ciy185","article-title":"A fungal immunotherapeutic vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial","volume":"66","author":"JE Edwards","year":"2018","journal-title":"Clin Infect Dis"},{"issue":"7395","key":"ppat.1014202.ref021","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nature10957","article-title":"Pathogen-induced human TH17 cells produce IFN-\u03b3 or IL-10 and are regulated by IL-1\u03b2","volume":"484","author":"CE Zielinski","year":"2012","journal-title":"Nature"},{"issue":"6","key":"ppat.1014202.ref022","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2019.01.041","article-title":"Human Anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans","volume":"176","author":"P Bacher","year":"2019","journal-title":"Cell"},{"issue":"7","key":"ppat.1014202.ref023","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0022770","article-title":"Th17 cells and IL-17 in protective immunity to vaginal candidiasis","volume":"6","author":"D Pietrella","year":"2011","journal-title":"PLoS One"},{"issue":"9","key":"ppat.1014202.ref024","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":"BM Peters","year":"2020","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1014202.ref025","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00182-15","article-title":"Transcriptomic analysis of vulvovaginal candidiasis identifies a role for the NLRP3 inflammasome","volume":"6","author":"VM Bruno","year":"2015","journal-title":"mBio"},{"key":"ppat.1014202.ref026","doi-asserted-by":"crossref","first-page":"100266","DOI":"10.1016\/j.lanepe.2021.100266","article-title":"Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources","volume":"13","author":"L Davidson","year":"2021","journal-title":"Lancet Reg Health Eur"},{"issue":"10","key":"ppat.1014202.ref027","doi-asserted-by":"crossref","DOI":"10.1002\/eji.70065","article-title":"Abundant yet aberrant T helper cell responses to Candida albicans underlie mucosal candidiasis in humans and mice","volume":"55","author":"C Basso","year":"2025","journal-title":"Eur J Immunol"},{"issue":"3","key":"ppat.1014202.ref028","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1010363","article-title":"Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development","volume":"18","author":"Y Manickam","year":"2022","journal-title":"PLoS Pathog"},{"key":"ppat.1014202.ref029","doi-asserted-by":"crossref","first-page":"109487","DOI":"10.1016\/j.intimp.2022.109487","article-title":"Halofuginone ameliorates systemic lupus erythematosus by targeting Blk in myeloid-derived suppressor cells","volume":"114","author":"J Ni","year":"2023","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"ppat.1014202.ref030","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11908-010-0143-y","article-title":"Prospects for development of a vaccine to prevent and control vaginal candidiasis","volume":"13","author":"PL Fidel","year":"2011","journal-title":"Curr Infect Dis Rep"},{"issue":"9","key":"ppat.1014202.ref031","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0046311","article-title":"The acute neutrophil response mediated by S100 alarmins during vaginal Candida infections is independent of the Th17-pathway","volume":"7","author":"J Yano","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"ppat.1014202.ref032","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.4049\/jimmunol.180.6.4022","article-title":"Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection","volume":"180","author":"S Bozza","year":"2008","journal-title":"J Immunol"},{"key":"ppat.1014202.ref033","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.3389\/fmicb.2019.02669","article-title":"A Role for Yeast\/Pseudohyphal Cells of Candida albicans in the Correlated Expression of NLRP3 Inflammasome Inducers in Women With Acute Vulvovaginal Candidiasis","volume":"10","author":"E Roselletti","year":"2019","journal-title":"Front Microbiol"},{"issue":"1","key":"ppat.1014202.ref034","doi-asserted-by":"crossref","first-page":"17877","DOI":"10.1038\/s41598-017-17649-8","article-title":"NLRP3 inflammasome is a key player in human vulvovaginal disease caused by Candida albicans","volume":"7","author":"E Roselletti","year":"2017","journal-title":"Sci Rep"},{"issue":"2","key":"ppat.1014202.ref035","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.chom.2015.07.004","article-title":"Pathogenic NLRP3 inflammasome activity during candida infection is negatively regulated by IL-22 via activation of NLRC4 and IL-1Ra","volume":"18","author":"M Borghi","year":"2015","journal-title":"Cell Host Microbe"},{"issue":"5","key":"ppat.1014202.ref036","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s10096-016-2600-5","article-title":"Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC","volume":"35","author":"M Jaeger","year":"2016","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"3","key":"ppat.1014202.ref037","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.03409-23","article-title":"Nanobody-mediated neutralization of candidalysin prevents epithelial damage and inflammatory responses that drive vulvovaginal candidiasis pathogenesis","volume":"15","author":"M Valentine","year":"2024","journal-title":"mBio"},{"issue":"9","key":"ppat.1014202.ref038","article-title":"A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis","volume":"17","author":"J Liu","year":"2021","journal-title":"PLoS Pathog"},{"issue":"2","key":"ppat.1014202.ref039","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1084\/jem.20081463","article-title":"Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis","volume":"206","author":"HR Conti","year":"2009","journal-title":"J Exp Med"},{"issue":"3","key":"ppat.1014202.ref040","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1365-2567.2009.03240.x","article-title":"Interleukin-17 and its target genes: Mechanisms of interleukin-17 function in disease","volume":"129","author":"RM Onishi","year":"2010","journal-title":"Immunology"},{"key":"ppat.1014202.ref041","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev-immunol-101819-092536","article-title":"IL-17 in the pathogenesis of disease: Good intentions gone awry","volume":"39","author":"S Majumder","year":"2021","journal-title":"Annu Rev Immunol"},{"issue":"1","key":"ppat.1014202.ref042","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1038\/s41467-022-33327-4","article-title":"IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis","volume":"13","author":"N Millet","year":"2022","journal-title":"Nat Commun"},{"issue":"12","key":"ppat.1014202.ref043","article-title":"IL-23 supports host defense against systemic Candida albicans infection by ensuring myeloid cell survival","volume":"15","author":"S Nur","year":"2019","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1014202.ref044","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004276","article-title":"Syk signaling in dendritic cells orchestrates innate resistance to systemic fungal infection","volume":"10","author":"PG Whitney","year":"2014","journal-title":"PLoS Pathog"},{"issue":"3","key":"ppat.1014202.ref045","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.immuni.2015.08.016","article-title":"Nociceptive sensory fibers drive interleukin-23 production from CD301b+ dermal dendritic cells and drive protective cutaneous immunity","volume":"43","author":"SW Kashem","year":"2015","journal-title":"Immunity"},{"issue":"1","key":"ppat.1014202.ref046","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrd4176","article-title":"Therapeutic opportunities of the IL-22-IL-22R1 system","volume":"13","author":"R Sabat","year":"2014","journal-title":"Nat Rev Drug Discov"},{"issue":"10","key":"ppat.1014202.ref047","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1084\/jem.20061308","article-title":"Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides","volume":"203","author":"SC Liang","year":"2006","journal-title":"J Exp Med"},{"issue":"7","key":"ppat.1014202.ref048","article-title":"Combinatorial actions of IL-22 and IL-17 drive optimal immunity to oral candidiasis through SPRRs","volume":"20","author":"FEY Aggor","year":"2024","journal-title":"PLoS Pathog"},{"issue":"4","key":"ppat.1014202.ref049","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/mi.2010.22","article-title":"IL-22 defines a novel immune pathway of antifungal resistance","volume":"3","author":"A De Luca","year":"2010","journal-title":"Mucosal Immunol"},{"issue":"11","key":"ppat.1014202.ref050","doi-asserted-by":"crossref","first-page":"5636","DOI":"10.4049\/jimmunol.1200594","article-title":"A novel Th cell epitope of Candida albicans mediates protection from fungal infection","volume":"188","author":"E B\u00e4r","year":"2012","journal-title":"J Immunol"},{"issue":"2","key":"ppat.1014202.ref051","doi-asserted-by":"crossref","first-page":"521","DOI":"10.4049\/jimmunol.1202924","article-title":"Cutting edge: IL-17-secreting innate lymphoid cells are essential for host defense against fungal infection","volume":"190","author":"A Gladiator","year":"2013","journal-title":"J Immunol"},{"issue":"6","key":"ppat.1014202.ref052","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1189\/jlb.4A0915-428R","article-title":"Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis","volume":"99","author":"N Whibley","year":"2016","journal-title":"J Leukoc Biol"},{"issue":"4","key":"ppat.1014202.ref053","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.immuni.2019.03.021","article-title":"The IL-17 family of cytokines in health and disease","volume":"50","author":"MJ McGeachy","year":"2019","journal-title":"Immunity"},{"key":"ppat.1014202.ref054","first-page":"17","article-title":"Biology of IL-22","volume":"32","author":"K Wolk","year":"2010","journal-title":"Semin Immunol"},{"issue":"2","key":"ppat.1014202.ref055","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1128\/IAI.01417-13","article-title":"Fungal morphogenetic pathways are required for the hallmark inflammatory response during Candida albicans vaginitis","volume":"82","author":"BM Peters","year":"2014","journal-title":"Infect Immun"},{"issue":"3","key":"ppat.1014202.ref056","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.immuni.2016.02.007","article-title":"Intestinal interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation","volume":"44","author":"P Kumar","year":"2016","journal-title":"Immunity"},{"issue":"3","key":"ppat.1014202.ref057","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1128\/CMR.9.3.335","article-title":"Immunopathogenesis of recurrent vulvovaginal candidiasis","volume":"9","author":"PL Fidel","year":"1996","journal-title":"Clin Microbiol Rev"},{"key":"ppat.1014202.ref058","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0923-2494(98)80760-8","article-title":"Protective immunity in experimental Candida vaginitis","volume":"149","author":"PL Fidel","year":"1998","journal-title":"Res Immunol"},{"issue":"1","key":"ppat.1014202.ref059","doi-asserted-by":"crossref","first-page":"110183","DOI":"10.1016\/j.celrep.2021.110183","article-title":"Estrogen promotes innate immune evasion of Candida albicans through inactivation of the alternative complement system","volume":"38","author":"P Kumwenda","year":"2022","journal-title":"Cell Rep"},{"key":"ppat.1014202.ref060","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.abb.2018.12.028","article-title":"17-\u03b2-estradiol enhances neutrophil extracellular trap formation by interaction with estrogen membrane receptor","volume":"663","author":"H Yasuda","year":"2019","journal-title":"Arch Biochem Biophys"},{"issue":"1","key":"ppat.1014202.ref061","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1128\/EC.5.1.180-191.2006","article-title":"Cellular and molecular biology of Candida albicans estrogen response","volume":"5","author":"G Cheng","year":"2006","journal-title":"Eukaryot Cell"},{"issue":"2","key":"ppat.1014202.ref062","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/1753425912454026","article-title":"Mouse estrous cycle regulation of vaginal versus uterine cytokines, chemokines, \u03b1-\/\u03b2-defensins and TLRs","volume":"19","author":"DK Hickey","year":"2013","journal-title":"Innate Immun"},{"issue":"20","key":"ppat.1014202.ref063","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.177899","article-title":"Progesterone promotes CXCl2-dependent vaginal neutrophil killing by activating cervical resident macrophage-neutrophil crosstalk","volume":"9","author":"C G\u00f3mez-Oro","year":"2024","journal-title":"JCI Insight"},{"issue":"8041","key":"ppat.1014202.ref064","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41586-024-08131-3","article-title":"Rhythmic IL-17 production by \u03b3\u03b4 T cells maintains adipose de novo lipogenesis","volume":"636","author":"A Douglas","year":"2024","journal-title":"Nature"},{"issue":"4","key":"ppat.1014202.ref065","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035538","article-title":"Mouse estrous cycle identification tool and images","volume":"7","author":"SL Byers","year":"2012","journal-title":"PLoS One"},{"issue":"13","key":"ppat.1014202.ref066","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1097\/QAD.0b013e32836290b6","article-title":"Hormonal contraception decreases bacterial vaginosis but oral contraception may increase candidiasis: Implications for HIV transmission","volume":"27","author":"JHHM van de Wijgert","year":"2013","journal-title":"AIDS"},{"issue":"3","key":"ppat.1014202.ref067","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/infdis\/jiv402","article-title":"Sex hormones coordinate neutrophil immunity in the vagina by controlling chemokine gradients","volume":"213","author":"S Lasarte","year":"2016","journal-title":"J Infect Dis"},{"key":"ppat.1014202.ref068","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.3389\/fimmu.2018.01033","article-title":"Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability to Candida albicans","volume":"9","author":"L Salinas-Mu\u00f1oz","year":"2018","journal-title":"Front Immunol"},{"issue":"6","key":"ppat.1014202.ref069","doi-asserted-by":"crossref","first-page":"618","DOI":"10.3390\/pathogens11060618","article-title":"Role of vaginal mucosa, host immunity and microbiota in vulvovaginal candidiasis","volume":"11","author":"SN Balakrishnan","year":"2022","journal-title":"Pathogens"},{"issue":"6","key":"ppat.1014202.ref070","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/emmm.201201678","article-title":"Genetic susceptibility to Candida infections","volume":"5","author":"SP Smeekens","year":"2013","journal-title":"EMBO Mol Med"},{"issue":"2","key":"ppat.1014202.ref071","doi-asserted-by":"crossref","first-page":"144","DOI":"10.3390\/microorganisms8020144","article-title":"Recurrent Vulvovaginal Candidiasis: An Immunological Perspective","volume":"8","author":"D Rosati","year":"2020","journal-title":"Microorganisms"},{"issue":"48","key":"ppat.1014202.ref072","article-title":"Oral epithelial IL-22\/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis","volume":"5","author":"FEY Aggor","year":"2020","journal-title":"Sci Immunol"},{"issue":"8","key":"ppat.1014202.ref073","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12841","article-title":"Identification of Candida albicans regulatory genes governing mucosal infection","volume":"20","author":"J Meir","year":"2018","journal-title":"Cell Microbiol"},{"issue":"1","key":"ppat.1014202.ref074","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41564-025-02198-y","article-title":"IL-17-mediated antifungal immunity restricts Candida albicans pathogenicity in the oral cavity","volume":"11","author":"R Fr\u00f3is-Martins","year":"2026","journal-title":"Nat Microbiol"},{"issue":"17","key":"ppat.1014202.ref075","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":"AH Verma","year":"2017","journal-title":"Sci Immunol"},{"issue":"2","key":"ppat.1014202.ref076","doi-asserted-by":"crossref","first-page":"627","DOI":"10.4049\/jimmunol.1800515","article-title":"IL-36 and IL-1\/IL-17 drive immunity to oral candidiasis via parallel mechanisms","volume":"201","author":"AH Verma","year":"2018","journal-title":"J Immunol"},{"issue":"9","key":"ppat.1014202.ref077","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005882","article-title":"IL-1 coordinates the neutrophil response to c. albicans in the oral mucosa","volume":"12","author":"S Altmeier","year":"2016","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1014202.ref078","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1038\/s41467-025-57797-4","article-title":"IL-1 protects from fatal systemic candidiasis in mice by inhibiting oxidative phosphorylation and hypoxia","volume":"16","author":"S Horn","year":"2025","journal-title":"Nat Commun"},{"issue":"5","key":"ppat.1014202.ref079","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005589","article-title":"Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway","volume":"12","author":"VC Anipindi","year":"2016","journal-title":"PLoS Pathog"},{"key":"ppat.1014202.ref080","doi-asserted-by":"crossref","first-page":"595936","DOI":"10.3389\/fimmu.2020.595936","article-title":"IL-1\u03b2-MyD88-mTOR axis promotes immune-protective IL-17A()Foxp3() cells during mucosal infection and is dysregulated with aging","volume":"11","author":"N Bhaskaran","year":"2020","journal-title":"Front Immunol"},{"issue":"10","key":"ppat.1014202.ref081","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1016\/j.celrep.2018.02.044","article-title":"IL-23 and IL-1\u03b2 Drive Human Th17 cell differentiation and metabolic reprogramming in absence of CD28 costimulation","volume":"22","author":"S Revu","year":"2018","journal-title":"Cell Rep"},{"issue":"3","key":"ppat.1014202.ref082","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/blood-2009-08-236521","article-title":"Regulating human Th17 cells via differential expression of IL-1 receptor","volume":"115","author":"W-W Lee","year":"2010","journal-title":"Blood"},{"issue":"4","key":"ppat.1014202.ref083","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.immuni.2008.03.001","article-title":"Th17 cell differentiation: the long and winding road","volume":"28","author":"MJ McGeachy","year":"2008","journal-title":"Immunity"},{"issue":"8","key":"ppat.1014202.ref084","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.4049\/jimmunol.2400510","article-title":"IL-17: A critical cytokine for defense against oral candidiasis","volume":"213","author":"L Dos Santos Dias","year":"2024","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1014202.ref085","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.coi.2010.06.009","article-title":"Inborn errors of mucocutaneous immunity to Candida albicans in humans: a role for IL-17 cytokines?","volume":"22","author":"A Puel","year":"2010","journal-title":"Curr Opin Immunol"},{"issue":"4","key":"ppat.1014202.ref086","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.immuni.2013.09.002","article-title":"An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis","volume":"39","author":"B Boisson","year":"2013","journal-title":"Immunity"},{"issue":"5","key":"ppat.1014202.ref087","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1084\/jem.20141065","article-title":"Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis","volume":"212","author":"Y Ling","year":"2015","journal-title":"J Exp Med"},{"issue":"6526","key":"ppat.1014202.ref088","doi-asserted-by":"crossref","DOI":"10.1126\/science.aay5731","article-title":"Aberrant type 1 immunity drives susceptibility to mucosal fungal infections","volume":"371","author":"TJ Break","year":"2021","journal-title":"Science"},{"issue":"4","key":"ppat.1014202.ref089","article-title":"Card9 deficiency exacerbates vulvovaginal candidiasis by impairing the IL-17 production and vaginal epithelial barrier","volume":"63","author":"W Liu","year":"2025","journal-title":"Med Mycol"},{"issue":"3","key":"ppat.1014202.ref090","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1095\/biolreprod.104.029603","article-title":"Interleukin (IL)-1, IL-6, and IL-8 predict mucosal toxicity of vaginal microbicidal contraceptives","volume":"71","author":"RN Fichorova","year":"2004","journal-title":"Biol Reprod"},{"issue":"2","key":"ppat.1014202.ref091","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1128\/IAI.70.2.577-583.2002","article-title":"Cytokine and chemokine production by human oral and vaginal epithelial cells in response to Candida albicans","volume":"70","author":"C Steele","year":"2002","journal-title":"Infect Immun"},{"issue":"3","key":"ppat.1014202.ref092","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.immuni.2011.03.002","article-title":"CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection model","volume":"34","author":"P Pandiyan","year":"2011","journal-title":"Immunity"},{"issue":"5","key":"ppat.1014202.ref093","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/mi.2012.128","article-title":"Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections","volume":"6","author":"N Hern\u00e1ndez-Santos","year":"2013","journal-title":"Mucosal Immunol"},{"issue":"6","key":"ppat.1014202.ref094","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1128\/IAI.67.6.3135-3140.1999","article-title":"Analysis of vaginal cell populations during experimental vaginal candidiasis","volume":"67","author":"PL Fidel","year":"1999","journal-title":"Infect Immun"},{"issue":"11","key":"ppat.1014202.ref095","doi-asserted-by":"crossref","first-page":"7162","DOI":"10.1128\/IAI.69.11.7162-7164.2001","article-title":"Resistance of T-cell receptor delta-chain-deficient mice to experimental Candida albicans vaginitis","volume":"69","author":"FL Wormley","year":"2001","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1014202.ref096","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/s41385-020-0305-7","article-title":"\u03b3\u03b4 T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis","volume":"13","author":"L Monin","year":"2020","journal-title":"Mucosal Immunol"},{"issue":"1","key":"ppat.1014202.ref097","doi-asserted-by":"crossref","DOI":"10.1093\/discim\/kyae004","article-title":"Gamma delta (\u03b3\u03b4) T cells in the female reproductive tract: Active participants or indifferent bystanders in reproductive success?","volume":"3","author":"KL Foyle","year":"2024","journal-title":"Discov Immunol"},{"issue":"7","key":"ppat.1014202.ref098","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/icb.2016.48","article-title":"The majority of murine \u03b3\u03b4 T cells at the maternal-fetal interface in pregnancy produce IL-17","volume":"94","author":"GV Pinget","year":"2016","journal-title":"Immunol Cell Biol"},{"issue":"7","key":"ppat.1014202.ref099","doi-asserted-by":"crossref","first-page":"317","DOI":"10.4049\/immunohorizons.1900040","article-title":"IL-17 Production by \u03b3\u03b4+ T Cells Is Critical for Inducing Th17 Responses in the Female Genital Tract and Regulated by Estradiol and Microbiota","volume":"3","author":"VC Anipindi","year":"2019","journal-title":"Immunohorizons"},{"issue":"2","key":"ppat.1014202.ref100","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.immuni.2009.08.001","article-title":"Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity","volume":"31","author":"CE Sutton","year":"2009","journal-title":"Immunity"},{"key":"ppat.1014202.ref101","doi-asserted-by":"crossref","first-page":"7464","DOI":"10.1038\/ncomms8464","article-title":"IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2(+)V\u03b36(+)\u03b3\u03b4 T cells","volume":"6","author":"A Akitsu","year":"2015","journal-title":"Nat Commun"},{"key":"ppat.1014202.ref102","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.imlet.2012.05.006","article-title":"Pathological effect of IL-17A-producing TCR\u03b3\u03b4(+) T cells in mouse genital mucosa against HSV-2 infection","volume":"147","author":"J-O Kim","year":"2012","journal-title":"Immunol Lett"},{"issue":"6","key":"ppat.1014202.ref103","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nm0695-552","article-title":"Gamma delta T cell-induced nitric oxide production enhances resistance to mucosal candidiasis","volume":"1","author":"J Jones-Carson","year":"1995","journal-title":"Nat Med"},{"issue":"10","key":"ppat.1014202.ref104","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1038\/s41564-025-02122-4","article-title":"Dynamic expression of candidalysin facilitates oral colonization of Candida albicans in mice","volume":"10","author":"R Fr\u00f3is-Martins","year":"2025","journal-title":"Nat Microbiol"},{"issue":"725","key":"ppat.1014202.ref105","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adi3363","article-title":"Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein","volume":"15","author":"E Roselletti","year":"2023","journal-title":"Sci Transl Med"},{"issue":"1","key":"ppat.1014202.ref106","doi-asserted-by":"crossref","first-page":"14095","DOI":"10.1038\/s41598-019-50410-x","article-title":"Diversity of vaginal microbiome and metabolome during genital infections","volume":"9","author":"C Ceccarani","year":"2019","journal-title":"Sci Rep"},{"issue":"2","key":"ppat.1014202.ref107","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00211-17","article-title":"Vaginal heparan sulfate linked to neutrophil dysfunction in the acute inflammatory response associated with experimental vulvovaginal Candidiasis","volume":"8","author":"J Yano","year":"2017","journal-title":"mBio"},{"issue":"1","key":"ppat.1014202.ref108","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1189\/jlb.1110645","article-title":"Estradiol impairs the Th17 immune response against Candida albicans","volume":"91","author":"M Relloso","year":"2012","journal-title":"J Leukoc Biol"},{"issue":"8","key":"ppat.1014202.ref109","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1128\/AAC.01564-08","article-title":"Antifungal activity of tamoxifen: In vitro and in vivo activities and mechanistic characterization","volume":"53","author":"K Dolan","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"issue":"5","key":"ppat.1014202.ref110","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1128\/IAI.01544-15","article-title":"Experimental models of vaginal candidiasis and their relevance to human Candidiasis","volume":"84","author":"A Cassone","year":"2016","journal-title":"Infect Immun"},{"key":"ppat.1014202.ref111","doi-asserted-by":"crossref","first-page":"692491","DOI":"10.3389\/fmicb.2021.692491","article-title":"It takes two to tango: how a dysregulation of the innate immunity, coupled with Candida virulence, triggers VVC onset","volume":"12","author":"A Ardizzoni","year":"2021","journal-title":"Front Microbiol"},{"issue":"4","key":"ppat.1014202.ref112","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.01286-22","article-title":"Microbiota of the Pregnant Mouse: Characterization of the Bacterial Communities in the Oral Cavity, Lung, Intestine, and Vagina through Culture and DNA Sequencing","volume":"10","author":"JM Greenberg","year":"2022","journal-title":"Microbiol Spectr"},{"issue":"9","key":"ppat.1014202.ref113","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1084\/jem.187.9.1463","article-title":"Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha\/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion","volume":"187","author":"R Horai","year":"1998","journal-title":"J Exp Med"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1014202","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:47:47Z","timestamp":1778608067000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014202"}},"subtitle":[],"editor":[{"given":"Joshua J.","family":"Obar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":113,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014202","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]}}}