Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 1UL, UK.
Protein Phosphorylation Lab, The Francis Crick Institute, London NW1 1AT, UK.
Cells. 2020 Mar 12;9(3):699. doi: 10.3390/cells9030699.
Host released alarmins and antimicrobial peptides (AMPs) are highly effective as antifungal agents and inducers. Whilst some are expressed constitutively at mucosal tissues, the primary site of many infections, others are elicited in response to pathogens. In the context of , the fungal factors inducing the release of these innate immune molecules are poorly defined. Herein, we identify candidalysin as a potent trigger of several key alarmins and AMPs known to possess potent anti- functions. We also find extracellular ATP to be an important activator of candidalysin-induced epithelial signalling responses, namely epidermal growth factor receptor (EGFR) and MAPK signalling, which mediate downstream innate immunity during oral epithelial infection. The data provide novel mechanistic insight into the induction of multiple key alarmins and AMPs, important for antifungal defences against .
宿主释放的警报素和抗菌肽(AMPs)作为抗真菌剂和诱导剂非常有效。虽然有些在黏膜组织(许多感染的主要部位)中持续表达,但其他则是针对病原体而产生的。在 的背景下,诱导这些先天免疫分子释放的真菌因素还没有得到很好的定义。在此,我们发现念珠菌溶素是几种已知具有强大抗 功能的关键警报素和 AMP 的有效触发剂。我们还发现细胞外 ATP 是念珠菌溶素诱导上皮信号反应(即表皮生长因子受体(EGFR)和 MAPK 信号)的重要激活剂,这些反应介导了口腔上皮感染期间下游的先天免疫。这些数据为多种关键警报素和 AMP 的诱导提供了新的机制见解,这些警报素和 AMP 对针对 的抗真菌防御至关重要。