Jennifer J Patitz, Natalie E Nieuwenhuizen, Anastasia Solomatina, Yann Bachelot, Thomas Krüger, Carl-Magnus Svensson, Stephanie Hoeppener, Ann-Kathrin Zimmermann, Matthew G Blango, Ronny Martin, Olaf Kniemeyer, Theresa Lange, Axel A Brakhage, Marc Thilo Figge, Oliver Kurzai, Kerstin Hünniger-Ast
Neutrophils effectively eliminate Candida albicans from human blood, but a subset of fungal cells escapes clearance and remains extracellular and viable. Here we show that this evasion is independent of known immune-escape traits of C. albicans. Instead, neutrophil-derived extracellular vesicles (EVs) enriched in antimicrobial proteins and neutrophil surface markers (CD66b, CD45, CD63, and complement receptors CR1, CR3 and CR4) promote this state. Isolated EVs bound to C. albicans preferentially in a complement-dependent manner, and this binding was partially inhibited by anti-CD11b, supporting CR3 involvement. Despite their antimicrobial cargo, EVs did not impair fungal growth. Instead, EV coating reduced neutrophil phagocytosis in purified-cell and whole-blood settings. These findings reveal a dual role for neutrophil-derived EVs at the host-pathogen interface: although enriched for innate effector molecules with potential antifungal activity, their deposition on C. albicans does not impair growth but is associated with reduced phagocytosis and maintenance of an extracellular population.