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Vascelli, G.

Publications and source records attributed to Vascelli, G..

2 recordsLinked to original sources
bioRxiv2026

Local albumin excess exacerbates Candida albicans-induced inflammasome activation underlying the immunopathology of vulvovaginal candidiasis.

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. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/700771v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@f13fd5org.highwire.dtl.DTLVardef@95e58aorg.highwire.dtl.DTLVardef@11104dforg.highwire.dtl.DTLVardef@56e9be_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗
bioRxiv2026

α-1,3-Glucan-Driven Remodeling of the Conidial Cell Wall in an Aspergillus fumigatus Vaccine Strain Alters Innate Immune Recognition

Aspergillus fumigatus is a major cause of invasive aspergillosis in immunocompromised patients, where current antifungal therapies are limited by toxicity, drug resistance, and lack of durable protection, and no vaccines are available. A mutant lacking the sterylglucosidase-encoding gene (sglA) has emerged as a candidate that induces protective immune responses, but the structural basis for this phenotype remains unclear. Here, we use cellular solid-state NMR spectroscopy to compare the organization of the conidial cell wall in {Delta}sglA and its wild-type counterpart. The {Delta}sglA conidial cell wall displays extensive remodeling, including increased -1,3-glucan content and structural polymorphism, strengthened interactions with {beta}-glucans, reduced hydration, and restricted molecular motion, together consolidating a more rigid scaffold with limited {beta}-glucan accessibility. These structural changes are associated with altered neutrophil responses and a shift in innate immune signaling. This work links cell-wall reorganization to altered immune recognition in this vaccine candidate, with implications for future immunotherapeutic strategies. TEASERMolecular-level Insights from a fungal vaccine candidate show how cell-wall remodeling could affect immune response.

biochemistry↗