We sought for a role of secretory aspartyl proteinase 2, (Sap2), a major virulence trait of Candida albicans, in a murine experimental model of vaginal candidiasis. Injection of enzymatically active, full-length Sap2 into the mouse vagina caused local PMN (neutrophil) influx and accumulation of the inflammasome-dependent interleukin (IL)-1beta but not of inflammasome-independent TNFalpha. No inflammatory response was detected following treatment with a N-terminus-truncated, enzymatically-inactive tSap2. Anti-Sap2 antibodies, in particular Fab from a human combinatorial antibody library inhibited or abolished the inflammatory response, provided they were able, like Pepstatin A, a known Sap inhibitor, to inhibit Sap2 enzyme activity. The same antibodies and Pepstatin A also caused strong inhibition of neutrophil influx and cytokine production early during experimental vaginal infection by Candida albicans. Sap2 induced expression of activated caspase-1 in murine vaginal epithelial cells as well as in a human vaginal epithelial cell line and caspase-1 inhibition down-regulated IL-1beta and IL-18 production by the vaginal epithelial cells. Overall, the data demonstrate that Sap2 is a critical determinant of the acute inflammatory response by the epithelial cells in vaginal candidiasis, and support the notion that vaccine-induced or passively administered anti-Sap antibodies could control vaginal disease.
|Data di pubblicazione:||2015|
|Autore/i:||Pericolini Eva; Gabrielli Elena; Roselletti Elena; Luciano Eugenio; Sabbatini Samuele; Moser Christian; Vecchiarelli Anna; Cassone Antonio|
|Titolo:||A role for secretory aspartyl proteinase of Candida albicans in mouse vaginal inflammation and vaginal candidiasis|
|Nome del convegno:||Sixth FEBS Advanced Lecture Course. Human Fungal Pathogens Molecular Mechanisms of Host-Pathogen Interactions and Virulence|
|Luogo del convegno:||La Colle sur Loup, France|
|Data del convegno:||16-22 May 2015|
|Citazione:||A role for secretory aspartyl proteinase of Candida albicans in mouse vaginal inflammation and vaginal candidiasis / Pericolini Eva; Gabrielli Elena; Roselletti Elena; Luciano Eugenio; Sabbatini Samuele; Moser Christian; Vecchiarelli Anna; Cassone Antonio. - (2015). ((Intervento presentato al convegno Sixth FEBS Advanced Lecture Course. Human Fungal Pathogens Molecular Mechanisms of Host-Pathogen Interactions and Virulence tenutosi a La Colle sur Loup, France nel 16-22 May 2015.|
|Tipologia||Abstract in Atti di Convegno|
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