{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T02:46:32Z","timestamp":1793760392623,"version":"4.6.1"},"reference-count":145,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Vulvovaginal candidiasis (VVC) is a symptomatic inflammation of the vagina mainly caused by <jats:italic>C. albicans<\/jats:italic>. Other species, such as <jats:italic>C. parapsilosis<\/jats:italic>, <jats:italic>C. glabrata<\/jats:italic>, <jats:italic>C. tropicalis<\/jats:italic>, and <jats:italic>C. krusei<\/jats:italic>, are mainly associated to the recurrent form of the disease (RVVC), although with a lower frequency. In its yeast form, <jats:italic>C. albicans<\/jats:italic> is tolerated by the vaginal epithelium, but switching to the invasive hyphal form, co-regulated with the expression of genes encoding virulence factors such as secreted aspartyl proteases (Sap) and candidalysin, allows for tissue damage. Vaginal epithelial cells play an important role by impairing <jats:italic>C. albicans<\/jats:italic> tissue invasion through several mechanisms such as epithelial shedding, secretion of mucin and strong interepithelial cell connections. However, morphotype switching coupled to increasing of the fungal burden can overcome the tolerance threshold and trigger an intense inflammatory response. Pathological inflammation is believed to be facilitated by an altered vaginal microbiome, i.e., <jats:italic>Lactobacillus<\/jats:italic> dysbiosis. Notwithstanding the damage caused by the fungus itself, the host response to the fungus plays an important role in the onset of VVC, exacerbating fungal-mediated damage. This response can be triggered by host PRR-fungal PAMP interaction and other more complex mechanisms (i.e., Sap-mediated NLRP3 activation and candidalysin), ultimately leading to strong neutrophil recruitment. However, recruited neutrophils appear to be ineffective at reducing fungal burden and invasion; therefore, they seem to contribute more to the symptoms associated with vaginitis than to protection against the disease. Recently, two aspects of the vulvovaginal environment have been found to associate with VVC and induce neutrophil anergy <jats:italic>in vitro<\/jats:italic>: perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and heparan sulfate. Interestingly, CAGTA antibodies have also been found with higher frequency in VVC as compared to asymptomatic colonized women. This review highlights and discusses recent advances on understanding the VVC pathogenesis mechanisms as well as the role of host defenses during the disease.<\/jats:p>","DOI":"10.3389\/fmicb.2021.692491","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T05:36:01Z","timestamp":1623044161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":87,"title":["It Takes Two to Tango: How a Dysregulation of the Innate Immunity, Coupled With Candida Virulence, Triggers VVC Onset"],"prefix":"10.3389","volume":"12","author":[{"given":"Andrea","family":"Ardizzoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Pericolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/jof6040225","article-title":"Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) impair neutrophil candidacidal activity and are increased in the cellular fraction of vaginal samples from women with Vulvovaginal Candidiasis.","volume":"6","author":"Ardizzoni","year":"2020","journal-title":"J. Fungi Basel Switz."},{"key":"B2","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1086\/377234","article-title":"Relation between recurrent Vulvovaginal Candidiasis, vaginal concentrations of mannose-binding lectin, and a mannose-binding lectin gene polymorphism in Latvian women.","volume":"37","author":"Babula","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1086\/429246","article-title":"Frequency of interleukin-4 (IL-4) -589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent Vulvovaginal Candidiasis.","volume":"40","author":"Babula","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-8-116","article-title":"Processing of predicted substrates of fungal Kex2 proteinases from Candida albicans, C. glabrata, Saccharomyces cerevisiae and Pichia pastoris.","volume":"8","author":"Bader","year":"2008","journal-title":"BMC Microbiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.238","article-title":"Lactate signalling regulates fungal \u03b2-glucan masking and immune evasion.","volume":"2","author":"Ballou","year":"2016","journal-title":"Nat. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/0002-9378(90)91186-g","article-title":"A follow-up study of methods of contraception, sexual activity, and rates of trichomoniasis, candidiasis, and bacterial vaginosis.","volume":"163","author":"Barbone","year":"1990","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-018-0607-z","article-title":"Vulvovaginal Candidiasis: species distribution of Candida and their antifungal susceptibility pattern.","volume":"18","author":"Bitew","year":"2018","journal-title":"BMC Womens Health"},{"key":"B8","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.annepidem.2017.08.010","article-title":"Recurrent Vulvovaginal Candidiasis.","volume":"27","author":"Blostein","year":"2017","journal-title":"Ann. Epidemiol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/jof7020119","article-title":"Immune Sensing of Candida albicans.","volume":"7","author":"Bojang","year":"2021","journal-title":"J. Fungi Basel Switz."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02364","article-title":"Targeting the Aryl hydrocarbon receptor with indole-3-aldehyde protects from Vulvovaginal Candidiasis via the IL-22-IL-18 Cross-Talk.","volume":"10","author":"Borghi","year":"2019","journal-title":"Front. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.bjm.2016.09.006","article-title":"Prevalence of Candida spp. in cervical-vaginal samples and the in vitro susceptibility of isolates.","volume":"48","author":"Brandolt","year":"2017","journal-title":"Braz. J. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004356","article-title":"Adaptive prediction as a strategy in microbial infections.","volume":"10","author":"Brunke","year":"2014","journal-title":"PLoS Pathog."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e00182","DOI":"10.1128\/mBio.00182-15","article-title":"Transcriptomic analysis of Vulvovaginal Candidiasis identifies a role for the NLRP3 inflammasome.","volume":"6","author":"Bruno","year":"2015","journal-title":"mBio"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4136","DOI":"10.4049\/jimmunol.1202671","article-title":"An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to Candida albicans.","volume":"190","author":"Byrd","year":"2013","journal-title":"J. Immunol. Baltim. Md"},{"key":"B15","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/nrmicro732","article-title":"The damage-response framework of microbial pathogenesis.","volume":"1","author":"Casadevall","year":"2003","journal-title":"Nat. Rev. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3703","DOI":"10.1128\/IAI.67.8.3703-3713.1999","article-title":"Host-pathogen interactions: redefining the basic concepts of virulence and pathogenicity.","volume":"67","author":"Casadevall","year":"1999","journal-title":"Infect. Immun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1038\/nrmicro3156","article-title":"Development of vaccines for Candida albicans: fighting a skilled transformer.","volume":"11","author":"Cassone","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1111\/1471-0528.12994","article-title":"Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine prospects.","volume":"122","author":"Cassone","year":"2015","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1097\/QAD.0b013e3283536ba8","article-title":"Candida and candidiasis in HIV-infected patients: where commensalism, opportunistic behavior and frank pathogenicity lose their borders.","volume":"26","author":"Cassone","year":"2012","journal-title":"AIDS Lond. Engl."},{"key":"B20","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1086\/314871","article-title":"In Vitro and in vivo anticandidal activity of human immunodeficiency virus protease inhibitors.","volume":"180","author":"Cassone","year":"1999","journal-title":"J. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","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":"Cassone","year":"2016","journal-title":"Infect. Immun."},{"key":"B22","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.mycmed.2014.05.001","article-title":"In vitro susceptibility profile of 200 recent clinical isolates of Candida spp. to topical antifungal treatments of Vulvovaginal Candidiasis, the imidazoles and nystatin agents.","volume":"24","author":"Choukri","year":"2014","journal-title":"J. Mycol. Medicale"},{"key":"B23","doi-asserted-by":"publisher","first-page":"4514","DOI":"10.1128\/IAI.64.11.4514-4519.1996","article-title":"Evidence for degradation of gastrointestinal mucin by Candida albicans secretory aspartyl proteinase.","volume":"64","author":"Colina","year":"1996","journal-title":"Infect. Immun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1080\/mmy.40.4.383.386","article-title":"High rate of vaginal infections caused by non-C. albicans Candida species among asymptomatic women.","volume":"40","author":"Dan","year":"2002","journal-title":"Med. Mycol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"3399","DOI":"10.1128\/IAI.65.8.3399-3405.1997","article-title":"Protective role of antimannan and anti-aspartyl proteinase antibodies in an experimental model of Candida albicans vaginitis in rats.","volume":"65","author":"De Bernardis","year":"1997","journal-title":"Infect. Immun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/mmy\/myx139","article-title":"Candida vaginitis: virulence, host response and vaccine prospects.","volume":"56","author":"De Bernardis","year":"2018","journal-title":"Med. Mycol."},{"key":"B27","first-page":"1","article-title":"Human microbiota in health and disease.","volume":"3","author":"de Vos","year":"2012","journal-title":"SelfCare"},{"key":"B28","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cytogfr.2014.03.003","article-title":"PDGF receptor signaling networks in normal and cancer cells.","volume":"25","author":"Demoulin","year":"2014","journal-title":"Cytokine Growth Factor Rev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e339","DOI":"10.1016\/S1473-3099(18)30103-8","article-title":"Global burden of recurrent Vulvovaginal Candidiasis: a systematic review.","volume":"18","author":"Denning","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1128\/IAI.01092-12","article-title":"Growth of Candida albicans cells on the physiologically relevant carbon source lactate affects their recognition and phagocytosis by immune cells.","volume":"81","author":"Ene","year":"2013","journal-title":"Infect. Immun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1056\/NEJMoa0901053","article-title":"Human dectin-1 deficiency and mucocutaneous fungal infections.","volume":"361","author":"Ferwerda","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"B32","doi-asserted-by":"publisher","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":"Fidel","year":"2004","journal-title":"Trends Microbiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1600-0897.2006.00450.x","article-title":"History and update on host defense against vaginal candidiasis.","volume":"57","author":"Fidel","year":"2007","journal-title":"Am. J. Reprod. Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2939","DOI":"10.1128\/iai.72.5.2939-2946.2004","article-title":"An intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of Vulvovaginal Candidiasis.","volume":"72","author":"Fidel","year":"2004","journal-title":"Infect. Immun."},{"key":"B35","doi-asserted-by":"publisher","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":"Fidel","year":"1999","journal-title":"Infect. Immun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.trsl.2006.11.006","article-title":"Cleavage of E-cadherin: a mechanism for disruption of the intestinal epithelial barrier by Candida albicans.","volume":"149","author":"Frank","year":"2007","journal-title":"Transl. Res. J. Lab. Clin. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1128\/IAI.02895-14","article-title":"Induction of caspase-11 by aspartyl proteinases of Candida albicans and implication in promoting inflammatory response.","volume":"83","author":"Gabrielli","year":"2015","journal-title":"Infect. Immun."},{"key":"B38","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1080\/21505594.2016.1184385","article-title":"In vivo induction of neutrophil chemotaxis by secretory aspartyl proteinases of Candida albicans.","volume":"7","author":"Gabrielli","year":"2016","journal-title":"Virulence"},{"key":"B39","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1097\/00001648-199603000-00013","article-title":"Risk factors for Vulvovaginal Candidiasis: a case-control study among university students.","volume":"7","author":"Geiger","year":"1996","journal-title":"Epidemiol. Camb. Mass"},{"key":"B40","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1128\/cmr.13.1.122-143.2000","article-title":"Potential role of phospholipases in virulence and fungal pathogenesis.","volume":"13","author":"Ghannoum","year":"2000","journal-title":"Clin. Microbiol. Rev"},{"key":"B41","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.mib.2012.04.005","article-title":"Importance of the Candida albicans cell wall during commensalism and infection.","volume":"15","author":"Gow","year":"2012","journal-title":"Curr. Opin. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.039719","article-title":"Keeping Candida commensal: how lactobacilli antagonize pathogenicity of Candida albicans in an in vitro gut model.","volume":"12","author":"Graf","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/j.fertnstert.2015.10.010","article-title":"Gynecologic health and disease in relation to the microbiome of the female reproductive tract.","volume":"104","author":"Green","year":"2015","journal-title":"Fertil. Steril."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3635","DOI":"10.1099\/mic.0.039354-0","article-title":"Candida albicans forms biofilms on the vaginal mucosa.","volume":"156","author":"Harriott","year":"2010","journal-title":"Microbiol. Read. Engl."},{"key":"B45","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.tim.2011.07.004","article-title":"Importance of Candida-bacterial polymicrobial biofilms in disease.","volume":"19","author":"Harriott","year":"2011","journal-title":"Trends Microbiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/0002-9378(92)91368-k","article-title":"Characteristics of three vaginal flora patterns assessed by gram stain among pregnant women. Vaginal Infections and prematurity study group.","volume":"166","author":"Hillier","year":"1992","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/imm.13255","article-title":"Candida albicans and candidalysin in inflammatory disorders and cancer.","volume":"162","author":"Ho","year":"2021","journal-title":"Immunology"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09915-2","article-title":"Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor.","volume":"10","author":"Ho","year":"2019","journal-title":"Nat. Commun."},{"key":"B49","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s12275-016-5514-0","article-title":"Interaction of Candida albicans with host cells: virulence factors, host defense, escape strategies, and the microbiota.","volume":"54","author":"H\u00f6fs","year":"2016","journal-title":"J. Microbiol. Seoul Korea"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005644","article-title":"Neutrophil attack triggers extracellular trap-dependent candida cell wall remodeling and altered immune recognition.","volume":"12","author":"Hopke","year":"2016","journal-title":"PLoS Pathog."},{"key":"B51","doi-asserted-by":"publisher","first-page":"251","DOI":"10.4161\/viru.20010","article-title":"Regulation of phenotypic transitions in the fungal pathogen Candida albicans.","volume":"3","author":"Huang","year":"2012","journal-title":"Virulence"},{"key":"B52","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1111\/j.1600-0714.2012.01149.x","article-title":"Identification by DNA microarray of genes involved in Candida albicans-treated gingival epithelial cells.","volume":"41","author":"Ikuta","year":"2012","journal-title":"J. Oral Pathol. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2724","DOI":"10.1128\/IAI.00469-16","article-title":"Candida albicans pathogenesis: fitting within the host-microbe damage response framework.","volume":"84","author":"Jabra-Rizk","year":"2016","journal-title":"Infect. Immun."},{"key":"B54","doi-asserted-by":"publisher","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":"Jaeger","year":"2016","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar3558","article-title":"A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent Vulvovaginal Candidiasis.","volume":"11","author":"Jaeger","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1513\/pats.200510-110JH","article-title":"Fungal infections.","volume":"3","author":"Kauffman","year":"2006","journal-title":"Proc. Am. Thorac. Soc."},{"key":"B57","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s11908-010-0137-9","article-title":"Vulvovaginal Candidiasis caused by Non-albicans Candida species: new insights.","volume":"12","author":"Kennedy","year":"2010","journal-title":"Curr. Infect. Dis. Rep."},{"key":"B58","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1128\/IAI.27.2.667-674.1980","article-title":"Adherence of Candida albicans and other Candida species to mucosal epithelial cells.","volume":"27","author":"King","year":"1980","journal-title":"Infect. Immun."},{"key":"B59","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.coi.2012.04.007","article-title":"Immunity to fungi.","volume":"24","author":"LeibundGut-Landmann","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1111\/mmi.13475","article-title":"Lactic acid bacteria differentially regulate filamentation in two heritable cell types of the human fungal pathogen Candida albicans.","volume":"102","author":"Liang","year":"2016","journal-title":"Mol. Microbiol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.ijgo.2005.08.024","article-title":"Mannose-binding lectin and Vulvovaginal Candidiasis.","volume":"92","author":"Liu","year":"2006","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079812","article-title":"Diverse vaginal microbiomes in reproductive-age women with Vulvovaginal Candidiasis.","volume":"8","author":"Liu","year":"2013","journal-title":"PloS One"},{"key":"B63","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1101\/gr.187427.114","article-title":"New signaling pathways govern the host response to C. albicans infection in various niches.","volume":"25","author":"Liu","year":"2015","journal-title":"Genome Res."},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3402\/mehd.v26.27799","article-title":"Changes in vaginal microbiota following antimicrobial and probiotic therapy.","volume":"26","author":"Macklaim","year":"2015","journal-title":"Microb. Ecol. Health Dis."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1086\/599213","article-title":"Prospective study of vaginal bacterial flora and other risk factors for Vulvovaginal Candidiasis.","volume":"199","author":"McClelland","year":"2009","journal-title":"J. Infect. Dis."},{"key":"B66","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1080\/21505594.2015.1012981","article-title":"Candida albicans-epithelial interactions and pathogenicity mechanisms: scratching the surface.","volume":"6","author":"Moyes","year":"2015","journal-title":"Virulence"},{"key":"B67","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.chom.2010.08.002","article-title":"A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells.","volume":"8","author":"Moyes","year":"2010","journal-title":"Cell Host Microbe"},{"key":"B68","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/nature17625","article-title":"Candidalysin is a fungal peptide toxin critical for mucosal infection.","volume":"532","author":"Moyes","year":"2016","journal-title":"Nature"},{"key":"B69","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.micinf.2011.06.009","article-title":"Candida albicans interactions with epithelial cells and mucosal immunity.","volume":"13","author":"Naglik","year":"2011","journal-title":"Microbes Infect."},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004257","article-title":"Candida albicans pathogenicity and epithelial immunity.","volume":"10","author":"Naglik","year":"2014","journal-title":"PLoS Pathog."},{"key":"B71","doi-asserted-by":"publisher","first-page":"6206","DOI":"10.1128\/IAI.72.11.6206-6210.2004","article-title":"Regulation of Candida albicans morphogenesis by fatty acid metabolites.","volume":"72","author":"Noverr","year":"2004","journal-title":"Infect. Immun."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/10408418709104444","article-title":"Candida infections: an overview.","volume":"15","author":"Odds","year":"1987","journal-title":"Crit. Rev. Microbiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/cei.12301","article-title":"Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti-neutrophil cytoplasmic antibodies.","volume":"176","author":"Ohlsson","year":"2014","journal-title":"Clin. Exp. Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.idc.2006.07.004","article-title":"Invasive candidiasis.","volume":"20","author":"Pappas","year":"2006","journal-title":"Infect. Dis. Clin. North Am."},{"key":"B75","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/s0301-2115(00)00289-x","article-title":"Determinants of different Candida species infections of the genital tract in women. Sporachrom Study Geoup.","volume":"93","author":"Parazzini","year":"2000","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-26811-8","author":"Parimelazhagan","year":"2016","journal-title":"Pharmacological Assays of Plant-Based Natural Products."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1128\/EC.00165-09","article-title":"Transcriptional responses of Candida albicans to epithelial and endothelial cells.","volume":"8","author":"Park","year":"2009","journal-title":"Eukaryot. Cell"},{"key":"B78","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1067\/mob.2000.108857","article-title":"Epithelial cell layer thickness and immune cell populations in the normal human vagina at different stages of the menstrual cycle.","volume":"183","author":"Patton","year":"2000","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/s41564-021-00875-2","article-title":"Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells.","volume":"6","author":"Pekmezovic","year":"2021","journal-title":"Nat. Microbiol."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-015-0971-3","article-title":"Vaginal colonisation by probiotic lactobacilli and clinical outcome in women conventionally treated for bacterial vaginosis and yeast infection.","volume":"15","author":"Pendharkar","year":"2015","journal-title":"BMC Infect. Dis."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00724-15","article-title":"Secretory aspartyl proteinases cause vaginitis and can mediate vaginitis caused by Candida albicans in mice.","volume":"6","author":"Pericolini","year":"2015","journal-title":"mBio"},{"key":"B82","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1080\/21505594.2016.1213937","article-title":"Therapeutic activity of a Saccharomyces cerevisiae-based probiotic and inactivated whole yeast on vaginal candidiasis.","volume":"8","author":"Pericolini","year":"2017","journal-title":"Virulence"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0201436","article-title":"Epitope unmasking in Vulvovaginal Candidiasis is associated with hyphal growth and neutrophilic infiltration.","volume":"13","author":"Pericolini","year":"2018","journal-title":"PLoS One"},{"key":"B84","doi-asserted-by":"publisher","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":"2020","journal-title":"J. Infect. Dis."},{"key":"B85","doi-asserted-by":"publisher","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":"Peters","year":"","journal-title":"Infect. Immun."},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003965","article-title":"Candida vaginitis: when opportunism knocks, the host responds.","volume":"10","author":"Peters","year":"","journal-title":"PLoS Pathog."},{"key":"B87","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1128\/CMR.00029-06","article-title":"Epidemiology of invasive candidiasis: a persistent public health problem.","volume":"20","author":"Pfaller","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"B88","doi-asserted-by":"publisher","first-page":"e00669","DOI":"10.1128\/IAI.00669-17","article-title":"Coassociation between group B streptococcus and Candida albicans promotes interactions with vaginal epithelium.","volume":"86","author":"Pidwill","year":"2018","journal-title":"Infect. Immun."},{"key":"B89","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1002\/eji.201242691","article-title":"Secreted aspartic proteases of Candida albicans activate the NLRP3 inflammasome.","volume":"43","author":"Pietrella","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022770","article-title":"Th17 cells and IL-17 in protective immunity to vaginal candidiasis.","volume":"6","author":"Pietrella","year":"2011","journal-title":"PLoS One"},{"key":"B91","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1097\/ACI.0b013e328358cc0b","article-title":"Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis.","volume":"12","author":"Puel","year":"2012","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1007\/s00520-015-3035-8","article-title":"Influence of cancer treatment on the Candida albicans isolated from the oral cavities of cancer patients.","volume":"24","author":"Ramla","year":"2016","journal-title":"Support. Care Cancer"},{"key":"B93","doi-asserted-by":"publisher","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women.","volume":"108","author":"Ravel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B94","doi-asserted-by":"publisher","first-page":"e2178","DOI":"10.1128\/mBio.02178-17","article-title":"Processing of Candida albicans Ece1p Is critical for candidalysin maturation and fungal virulence.","volume":"9","author":"Richardson","year":"","journal-title":"mBio"},{"key":"B95","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1080\/21505594.2015.1004977","article-title":"Adaptive immune responses to Candida albicans infection.","volume":"6","author":"Richardson","year":"2015","journal-title":"Virulence"},{"key":"B96","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.semcdb.2018.02.026","article-title":"Candida innate immunity at the mucosa.","volume":"89","author":"Richardson","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"e645","DOI":"10.1128\/IAI.00645-17","article-title":"Candidalysin drives epithelial signaling, neutrophil recruitment, and immunopathology at the vaginal mucosa.","volume":"86","author":"Richardson","year":"","journal-title":"Infect. Immun."},{"key":"B98","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1128\/JCM.43.5.2155-2162.2005","article-title":"Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases.","volume":"43","author":"Richter","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"B99","doi-asserted-by":"publisher","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":"Roselletti","year":"","journal-title":"Front. Microbiol."},{"key":"B100","doi-asserted-by":"publisher","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":"Roselletti","year":"2017","journal-title":"Sci. Rep."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1093\/infdis\/jiz365","article-title":"Vaginal epithelial cells discriminate between yeast and hyphae of Candida albicans in women who are colonized or have vaginal candidiasis.","volume":"220","author":"Roselletti","year":"","journal-title":"J. Infect. Dis."},{"key":"B102","doi-asserted-by":"publisher","first-page":"11007","DOI":"10.1073\/pnas.1834481100","article-title":"Phagocytosis by neutrophils induces an amino acid deprivation response in Saccharomyces cerevisiae and Candida albicans.","volume":"100","author":"Rubin-Bejerano","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B103","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1111\/myc.12883","article-title":"Randomised clinical trial in women with recurrent Vulvovaginal Candidiasis: efficacy of probiotics and lactoferrin as maintenance treatment.","volume":"62","author":"Russo","year":"2019","journal-title":"Mycoses"},{"key":"B104","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1080\/13693780500434701","article-title":"Gene transcription studies of Candida albicans following infection of HEp2 epithelial cells.","volume":"44","author":"Sandovsky-Losica","year":"2006","journal-title":"Med. Mycol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1111\/j.1574-6941.2008.00561.x","article-title":"In vitro effects of selected synbiotics on the human faecal microbiota composition.","volume":"66","author":"Saulnier","year":"2008","journal-title":"FEMS Microbiol. Ecol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1099\/00221287-135-3-475","article-title":"Electron microscopy of adhesive interactions between gardnerella vaginalis and vaginal epithelial cells, McCoy cells and human red blood cells.","volume":"135","author":"Scott","year":"1989","journal-title":"J. Gen. Microbiol."},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00437","article-title":"The fungal pathogen Candida albicans promotes bladder colonization of group B streptococcus.","volume":"9","author":"Shing","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1002\/emmm.201201678","article-title":"Genetic susceptibility to Candida infections.","volume":"5","author":"Smeekens","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"B109","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1113\/JP271694","article-title":"The vaginal microbiota, host defence and reproductive physiology.","volume":"595","author":"Smith","year":"2017","journal-title":"J. Physiol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1016\/S0140-6736(07)60917-9","article-title":"Vulvovaginal candidosis.","volume":"369","author":"Sobel","year":"2007","journal-title":"Lancet Lond. Engl."},{"key":"B111","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ajog.2015.06.067","article-title":"Recurrent Vulvovaginal Candidiasis.","volume":"214","author":"Sobel","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B112","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1128\/JCM.34.10.2497-2499.1996","article-title":"Vaginal microbiology of women with acute recurrent Vulvovaginal Candidiasis.","volume":"34","author":"Sobel","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/s0002-9378(98)80001-x","article-title":"Vulvovaginal Candidiasis: epidemiologic, diagnostic, and therapeutic considerations.","volume":"178","author":"Sobel","year":"1998","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1128\/IAI.00650-10","article-title":"Regulation of innate immune response to Candida albicans infections by \u03b1M\u03b22-Pra1p interaction.","volume":"79","author":"Soloviev","year":"2011","journal-title":"Infect. Immun."},{"key":"B115","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/nrmicro.2017.58","article-title":"The resilience of the intestinal microbiota influences health and disease.","volume":"15","author":"Sommer","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"B116","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/s0002-9378(99)70141-9","article-title":"Effect of antibiotic use on the prevalence of symptomatic Vulvovaginal Candidiasis.","volume":"180","author":"Spinillo","year":"1999","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1080\/10647440400028136","article-title":"The in vitro activity of vaginal Lactobacillus with probiotic properties against Candida.","volume":"13","author":"Strus","year":"2005","journal-title":"Infect. Dis. Obstet. Gynecol."},{"key":"B118","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/nrmicro2636","article-title":"Growth of Candida albicans hyphae.","volume":"9","author":"Sudbery","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"97.e1","DOI":"10.1016\/j.ajog.2007.06.039","article-title":"An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole.","volume":"198","author":"Swidsinski","year":"2008","journal-title":"Am. J. Obstet. Gynecol"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004948","article-title":"turning up the heat: inflammasome activation by fungal pathogens.","volume":"11","author":"Tavares","year":"2015","journal-title":"PLoS Pathog."},{"key":"B121","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1111\/j.1462-5822.2005.00659.x","article-title":"Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms.","volume":"8","author":"Urban","year":"2006","journal-title":"Cell. Microbiol."},{"key":"B122","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.it.2011.01.003","article-title":"Inflammasome activation and IL-1\u03b2 and IL-18 processing during infection.","volume":"32","author":"van de Veerdonk","year":"2011","journal-title":"Trends Immunol."},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105998","article-title":"The vaginal microbiota: what have we learned after a decade of molecular characterization?","volume":"9","author":"van de Wijgert","year":"2014","journal-title":"PLoS One"},{"key":"B124","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1159\/000293745","article-title":"Descriptive light and electron microscopy of normal and clue-cell-positive discharge.","volume":"25","author":"van der Meijden","year":"1988","journal-title":"Gynecol. Obstet. Invest."},{"key":"B125","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.tcb.2014.12.009","article-title":"Mechanisms of inflammasome activation: recent advances and novel insights.","volume":"25","author":"Vanaja","year":"2015","journal-title":"Trends Cell Biol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.2217\/FMB.15.52","article-title":"Experimental models of vaginal candidiasis and inflammation.","volume":"10","author":"Vecchiarelli","year":"2015","journal-title":"Future Microbiol."},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-020-01075-w","article-title":"Oral health problems among palliative and terminally ill patients: an integrated systematic review.","volume":"20","author":"Venkatasalu","year":"2020","journal-title":"BMC Oral Health"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036952","article-title":"Candida albicans-epithelial interactions: dissecting the roles of active penetration, induced endocytosis and host factors on the infection process.","volume":"7","author":"W\u00e4chtler","year":"2012","journal-title":"PLoS One"},{"key":"B129","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-3-642-39432-4_1","article-title":"\u201c1 from commensal to pathogen: Candida albicans,\u201d in","author":"Whittington","year":"2014","journal-title":"Human Fungal Pathogens"},{"key":"B130","doi-asserted-by":"publisher","first-page":"e527","DOI":"10.1128\/IAI.00527-18","article-title":"Comparative analysis of the capacity of the candida species to elicit vaginal immunopathology.","volume":"86","author":"Willems","year":"2018","journal-title":"Infect. Immun."},{"key":"B131","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1080\/21505594.2016.1230580","article-title":"A tale of two yeasts: saccharomyces cerevisiae as a therapeutic against candidiasis.","volume":"8","author":"Wilson","year":"2017","journal-title":"Virulence"},{"key":"B132","author":"Wilson","year":"2005","journal-title":"Microbial Inhabitants of Humans: their Ecology and Role in Health and Disease."},{"key":"B133","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1093\/infdis\/jiw201","article-title":"Streptococcus oralis and Candida albicans synergistically activate \u03bc-calpain to degrade E-cadherin from oral epithelial junctions.","volume":"214","author":"Xu","year":"2016","journal-title":"J. Infect. Dis."},{"key":"B134","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.3748\/wjg.v20.i12.3255","article-title":"Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease.","volume":"20","author":"Xu","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"B135","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.micres.2013.02.008","article-title":"Disruption of the intestinal mucosal barrier in Candida albicans infections.","volume":"168","author":"Yan","year":"2013","journal-title":"Microbiol. Res."},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.3791\/3382","article-title":"Protocols for vaginal inoculation and sample collection in the experimental mouse model of Candida vaginitis.","volume":"58","author":"Yano","year":"2011","journal-title":"J. Vis. Exp."},{"key":"B137","doi-asserted-by":"publisher","first-page":"5126","DOI":"10.1128\/IAI.00388-10","article-title":"Epithelial cell-derived S100 calcium-binding proteins as key mediators in the hallmark acute neutrophil response during Candida vaginitis.","volume":"78","author":"Yano","year":"2010","journal-title":"Infect. Immun."},{"key":"B138","doi-asserted-by":"publisher","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":"Yano","year":"2012","journal-title":"Cytokine"},{"key":"B139","doi-asserted-by":"publisher","first-page":"e211","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":"Yano","year":"2017","journal-title":"mBio"},{"key":"B140","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1128\/IAI.00861-13","article-title":"Vaginal epithelial cell-derived S100 alarmins induced by Candida albicans via pattern recognition receptor interactions are sufficient but not necessary for the acute neutrophil response during experimental vaginal candidiasis.","volume":"82","author":"Yano","year":"2014","journal-title":"Infect. Immun."},{"key":"B141","doi-asserted-by":"publisher","first-page":"e684","DOI":"10.1128\/IAI.00684-17","article-title":"Novel mechanism behind the immunopathogenesis of Vulvovaginal Candidiasis: \u201cNeutrophil Anergy\u201d.","volume":"86","author":"Yano","year":"2018","journal-title":"Infect. Immun"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-019-0748-8","article-title":"Current patient perspectives of Vulvovaginal Candidiasis: incidence, symptoms, management and post-treatment outcomes.","volume":"19","author":"Yano","year":"2019","journal-title":"BMC Womens Health"},{"key":"B143","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1111\/j.1462-5822.2007.01009.x","article-title":"In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination.","volume":"9","author":"Zakikhany","year":"2007","journal-title":"Cell. Microbiol."},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.3390\/jof6040348","article-title":"Human pathogenic Candida species respond distinctively to lactic acid stress.","volume":"6","author":"Zangl","year":"2020","journal-title":"J. Fungi Basel Switz"},{"key":"B145","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1099\/mic.0.26905-0","article-title":"Characterization of vaginal microbial communities in adult healthy women using cultivation-independent methods.","volume":"150","author":"Zhou","year":"2004","journal-title":"Microbiol. Read. Engl."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.692491\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T05:36:09Z","timestamp":1623044169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.692491\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":145,"alternative-id":["10.3389\/fmicb.2021.692491"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.692491","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,7]]},"article-number":"692491"}}