■我们先前发现,呼吸道上皮细胞可以通过将表达在GAS表面的纤连蛋白(Fn)结合蛋白(FnBp)与血浆蛋白Fn结合而诱导的自噬来消除侵袭的A族链球菌(GAS)及其受体整合素α5β1。FnBp+细菌通过FnBp-Fn-整合素α5β1轴启动的自噬是否是呼吸道上皮细胞的常见事件?
■我们选择了金黄色葡萄球菌(S.金黄色葡萄球菌/S.a)和单核细胞增生李斯特菌(L.单核细胞增多症/L.M)作为细胞外和细胞内FnBp+细菌的代表,分别。对它们的FnBp进行纯化,并通过蛋白质印迹确认蛋白功能,活细菌计数,共聚焦和下拉。通过IP检测到作用轴下游的关键分子,质谱和生物信息学分析。
■我们发现来自金黄色葡萄球菌和单核细胞增生李斯特菌的不同FnBp可以通过FnBp-Fn-整合素α5β1轴启动自噬,这可以被认为是一个普遍事件,宿主试图从上皮细胞中清除入侵的细菌。重要的是,我们首先报道了S100A8作为整合素β1链下游的关键分子,在整合素α5β1激活后高度表达,从而上调自噬。
■来自FnBp+细菌的各种FnBp具有通过FnBp-Fn-整合素α5β1轴启动自噬的能力,以促进在较少的入侵者存在下从上皮细胞中去除入侵细菌。S100A8是自噬途径中整合素α5β1下游的关键分子。
We previously found that the respiratory epithelial cells could eliminate the invaded group A streptococcus (GAS) through autophagy induced by binding a fibronectin (Fn) binding protein (
FnBp) expressed on the surface of GAS to plasma protein Fn and its receptor integrin α5β1 of epithelial cells. Is autophagy initiated by
FnBp+ bacteria via
FnBp-Fn-Integrin α5β1 axis a common event in respiratory epithelial cells?
We chose Staphylococcus aureus (S. aureus/S. a) and Listeria monocytogenes (L. monocytogenes/L. m) as representatives of extracellular and intracellular
FnBp+ bacteria, respectively. The
FnBp of them was purified and the protein function was confirmed by western blot, viable bacteria count, confocal and pull-down. The key molecule downstream of the action axis was detected by IP, mass spectrometry and bio-informatics analysis.
We found that different FnBp from both S. aureus and L. monocytogenes could initiate autophagy through FnBp-Fn-integrin α5β1 axis and this could be considered a universal event, by which host tries to remove invading bacteria from epithelial cells. Importantly, we firstly reported that S100A8, as a key molecule downstream of integrin β1 chain, is highly expressed upon activation of integrin α5β1, which in turn up-regulates autophagy.
Various
FnBp from
FnBp+ bacteria have the ability to initiate autophagy via
FnBp-Fn-Integrin α5β1 axis to promote the removal of invading bacteria from epithelial cells in the presence of fewer invaders. S100A8 is a key molecule downstream of Integrin α5β1 in this autophagy pathway.