Human Neutrophils Produce Antifungal Extracellular Vesicles against Aspergillus fumigatus
Iordana A. Shopova, I. A. Belyaev, Prasad Dasari, Susanne Jahreis, María C. Stroe, Zoltán Cseresnyés, Ann-Kathrin Zimmermann, Anna Medyukhina, Carl‐Magnus Svensson, Thomas Krüger, Viktória Szeifert, Sándor Nietzsche, Theresia Conrad, Matthew G. Blango, Olaf Kniemeyer, Marie von Lilienfeld‐Toal, Peter F. Zipfel, Erzsébet Ligeti, Marc Thilo Figge, Axel A. Brakhage
Abstract
Invasive fungal infections caused by the mold Aspergillus fumigatus are a growing concern in the clinic due to the increasing use of immunosuppressive therapies and increasing antifungal drug resistance. These infections result in high rates of mortality, as treatment and diagnostic options remain limited. In healthy individuals, neutrophilic granulocytes are critical for elimination of A. fumigatus from the host; however, the exact extracellular mechanism of neutrophil-mediated antifungal activity remains unresolved. Here, we present a mode of antifungal defense employed by human neutrophils against A. fumigatus not previously described. We found that extracellular vesicles produced by neutrophils in response to A. fumigatus infection are able to associate with the fungus, limit growth, and elicit cell damage by delivering antifungal cargo. In the end, antifungal extracellular vesicle biology provides a significant step forward in our understanding of A. fumigatus host pathogenesis and opens up novel diagnostic and therapeutic possibilities.