Human Epithelial Cells Discriminate between Commensal and Pathogenic Interactions with Candida albicans

The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage.

共生真菌白色念珠菌（Candida albicans）可在易感个体中引发危及生命的感染。多数人体内的白色念珠菌会定植于黏膜表面，黏附并与上皮细胞发生相互作用。低浓度的白色念珠菌无致病性，体外实验中亦不会造成上皮细胞损伤；而高浓度的白色念珠菌则会引发黏膜感染，并在体外环境中杀伤上皮细胞。本研究发现，尽管暴露于真菌的上皮细胞群体存在剂量依赖性的数量差异，但这实则反映了宿主细胞对白色念珠菌应答的根本性性质差异。本研究通过转录组分析实验与实时荧光定量PCR（real-time PCR）发现，野生型白色念珠菌可诱导FaDu上皮细胞系产生剂量依赖性应答。然而，通过使用高浓度的不同白色念珠菌菌株开展实时荧光定量PCR与蛋白质印迹（Western blot）分析，本研究证实这类剂量依赖性应答与宿主细胞损伤的促发能力密切相关。本研究结果支持以下观点：上皮细胞通过监测黏膜表面的微生物群落，并在群落功能失调时启动防御应答，在免疫系统中发挥关键作用。这使得上皮细胞在与白色念珠菌的互作中处于关键枢纽位置，因为上皮细胞自身会加剧白色念珠菌诱导的细胞损伤。