Induction of brain microvascular endothelial cell urokinase expression by Cryptococcus neoformans facilitates blood-brain barrier invasion.

摘要: The invasive ability of the blood-borne fungal pathogen Cryptococcus neoformans can be enhanced through interactions with host plasma components, such as plasminogen. Previously we showed by in vitro studies that plasminogen coats surface C. and is converted to active serine protease, plasmin, activators. Viable, but not formaldehyde- or sodium azide-killed, cryptococcal strains undergo brain microvascular endothelial cell-dependent plasminogen-to-plasmin activation, which results enhanced, plasmin-dependent invasion primary bovine cells degrade plasmin substrates. In present work, cultured viable, killed, led significant increases both urokinase mRNA transcription cell-associated protein expression. Soluble was also detected conditioned medium from neoformans. Exposure pre-coated viable strain-matched cell-fungal co-cultures resulted activation invasion. siRNA-mediated silencing gene expression use specific inhibitors activity abrogated on cryptococcal-brain cell Our suggest exploitation urokinase-plasmin(ogen) system may contribute virulence during cryptococcosis.