E GUIDUCCI ¹, S LEIBUNDGUT-LANDMANN<sup>1

1</sup>Section of Immunology, Vetsuisse Faculty, University of Zürich, Switzerland

NETs are web-like structures composed of decondensed chromatin and antimicrobial substances, which restrain and subsequently kill pathogens, including bacteria and fungi. NET formation is associated with citrullination of histone H3 by peptidyl arginine deiminase, type IV (PAD4), histone degradation by neutrophil elastase (NE) and myeloid peroxidases (MPO)-driven chromatin decondensation. PAD4 is expressed prominently in mature neutrophils and it has been shown to be central for NET formation, as PAD4 knockout mice show abolished induction of histone citrullination and fail to form NETs.
C. albicans hyphae (but not C. albicans yeast) can efficiently induce NET formation, as in vitro studies have shown. The observation that Candida hyphae are the predominant morphotype found in infected organs and that these structures are too large to be phagocytosed efficiently, suggests that NETs may also be relevant during infection in vivo. However, the contribution of NETs to fungal control and host protection has not been clarified. Using a mouse model of systemic candidiasis, we analysed citrullination of histone H3 in neutrophils in the infected kidney, the main target organ of C. albicans during infection, and found NETs to be strongly induced. Their abundance increased over time, paralleling the increase in neutrophil numbers and the presence of fungal hyphae. The relevance of NET induction during systemic candidiasis is also addressed in this project.