Resist or die: Identification and functional characterization of cell wall integrity determinants important for the survival of Aspergillus fumigatus challenged by neutrophil granulocytes.

空气传播的机会性真菌病原体烟曲霉会在免疫受损的宿主中引起严重的全身感染。中性粒细胞在防御这种霉菌引起的侵袭性感染中起着关键作用。粒细胞如何检测和杀死曲霉菌丝，特别是曲霉菌如何应对粒细胞触发的压力，其机制在很大程度上仍不清楚。利用一种新建立的杀伤实验，我们揭示了真菌应激反应途径在对抗人类粒细胞攻击方面的重要性。这项研究计划旨在确定和表征决定人粒细胞挑战的烟曲霉菌丝存活的新因素。我们将详细探讨保护霉菌菌丝的分子机制，研究对真菌细胞壁的影响，并通过研究菌丝对人类粒细胞的细胞反应来识别和研究进一步的信号途径和应激反应。我们的结果将进一步阐明中性粒细胞和曲霉菌丝之间的重要相互作用，并揭示治疗侵袭性真菌感染的新方法。

The airborne opportunistic fungal pathogen Aspergillus fumigatus causes severe systemic infections in the immunocompromised host. Neutrophil granulocytes play a key role in the defense against invasive infections caused by this mold. The mechanisms how granulocytes detect and kill Aspergillus hyphae and especially how Aspergillus copes with granulocyte-triggered stress remain largely uncharacterized. Using a newly established killing assay, we unveiled the importance of fungal stress response pathway to counter the attack of human granulocytes. This research proposal aims on identifying and characterizing novel factors that determine survival of A. fumigatus hyphae challenged by human granulocytes. We will explore the molecular mechanisms responsible for protecting the mold’s hyphae in detail, study the influence on the fungal cell wall and identify and investigate further signaling routs and stress responses by studying the cellular response of hyphae challenged by human granulocytes. Our results will shed more light on the important interaction of neutrophil granulocytes and Aspergillus hyphae and disclose novel therapeutic approaches to treat invasive fungal infections.