Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis.

Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis. Mark Gresnigt, Sophie Austermeier, Axel Dietschmann, Gianluca Vascelli, and 21 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8945772/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Vulvovaginal candidiasis (VVC) is a mucosal yeast infection where symptoms are driven by inflammatory responses. The onset of VVC is instigated by the yeast Candida albicans, but the underlying causes of disease-driving hyperinflammation remains incompletely resolved. We found that vaginal albumin concentrations are higher in women with recurrent VVC and during VVC in mice. These albumin levels correlated with inflammatory cytokines in vaginal lavages. While the abundance of this serum protein in the vagina can represent a hallmark of inflammation-induced vascular permeability, we reveal molecular mechanisms by which albumin also drives inflammation. It increased NLRP3 inflammasome activation in human macrophages elicited by C. albicans. Albumin induced fungal adaptations that increased resistance to macrophage-mediated clearance. Further it increased the expression of fungal secreted aspartic protease 1, which we identified as the effector driving inflammasome activation. Moreover, neutrophils show impaired effectivity in clearing C. albicans in presence of albumin. Collectively, vaginal albumin may not only be a consequence of inflammation of the vaginal mucosa, but also can drive hyperinflammatory responses that underlie immunopathology in VVC. Biological sciences/Microbiology/Fungi/Fungal host response Biological sciences/Immunology/Infectious diseases/Fungal infection Biological sciences/Microbiology/Fungi/Fungal immune evasion Biological sciences/Microbiology/Fungi/Fungal pathogenesis Biological sciences/Immunology/Inflammation/Inflammasome NLRP3 Inflammasome Candida albicans macrophages IL-1β secreted aspartic proteinases Full Text Additional Declarations Yes there is potential Competing Interest. G.G.G.D. is the chairperson of Femicare vzw and has worked as a medical consultant for various industries. None of these organizations or companies were involved in funding, the design, communication, or data analysis of this study. The other authors declare no competing interests and no conflicting financial interests. Supplementary Files AlbuminmanuscriptSupplement2026.pdf Supplementary figures Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8945772","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":596990555,"identity":"c70dca2d-15ff-471e-b785-a5f6d00d84c1","order_by":0,"name":"Mark Gresnigt","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-9514-4634","institution":"Leibniz Institute for Natural Product Research and Infection Biology - 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None of these organizations or companies were involved in funding, the design, communication, or data analysis of this study. The other authors declare no competing interests and no conflicting financial interests.","formattedTitle":"Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis.","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"NLRP3 Inflammasome, Candida albicans, macrophages, IL-1β, secreted aspartic proteinases","lastPublishedDoi":"10.21203/rs.3.rs-8945772/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8945772/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Vulvovaginal candidiasis (VVC) is a mucosal yeast infection where symptoms are driven by inflammatory responses. The onset of VVC is instigated by the yeast Candida albicans, but the underlying causes of disease-driving hyperinflammation remains incompletely resolved. We found that vaginal albumin concentrations are higher in women with recurrent VVC and during VVC in mice. These albumin levels correlated with inflammatory cytokines in vaginal lavages. While the abundance of this serum protein in the vagina can represent a hallmark of inflammation-induced vascular permeability, we reveal molecular mechanisms by which albumin also drives inflammation. It increased NLRP3 inflammasome activation in human macrophages elicited by C. albicans. Albumin induced fungal adaptations that increased resistance to macrophage-mediated clearance. Further it increased the expression of fungal secreted aspartic protease 1, which we identified as the effector driving inflammasome activation. Moreover, neutrophils show impaired effectivity in clearing C. albicans in presence of albumin. Collectively, vaginal albumin may not only be a consequence of inflammation of the vaginal mucosa, but also can drive hyperinflammatory responses that underlie immunopathology in VVC.","manuscriptTitle":"Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-26 03:31:30","doi":"10.21203/rs.3.rs-8945772/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"483c0baf-fc22-41e7-a6ee-3de5060f7ae0","owner":[],"postedDate":"February 26th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"revise","date":"2026-05-13T10:02:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-05-11T14:04:40+00:00","index":4,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-05-01T13:36:49+00:00","index":3,"fulltext":"This content is not available."}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":63525710,"name":"Biological sciences/Microbiology/Fungi/Fungal host response"},{"id":63525711,"name":"Biological sciences/Immunology/Infectious diseases/Fungal infection"},{"id":63525712,"name":"Biological sciences/Microbiology/Fungi/Fungal immune evasion"},{"id":63525713,"name":"Biological sciences/Microbiology/Fungi/Fungal pathogenesis"},{"id":63525714,"name":"Biological sciences/Immunology/Inflammation/Inflammasome"}],"tags":[],"updatedAt":"2026-05-13T10:06:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-26 03:31:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8945772","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8945772","identity":"rs-8945772","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}