Axsen Wendy S, Styer Cathy M, Solnick Jay V
Center for Comparative Medicine, University of California, Davis, CA 95616, USA.
Microb Pathog. 2009 Oct;47(4):231-6. doi: 10.1016/j.micpath.2009.08.002. Epub 2009 Aug 13.
Heat shock proteins (HSPs) are primarily known as molecular chaperones that are induced by cell stress and prevent protein aggregation and facilitate folding. Recent evidence suggests that exposure of cells to microbial pathogens can also induce HSPs, which then modulate both innate and adaptive immune responses. Paradoxically, Helicobacter pylori has been found to decrease expression of HSPs. We sought to investigate this phenomenon further and to examine the role of different H. pylori strains and recognized virulence factors in cell culture and in the mouse model. Co-culture of H. pylori with two gastric carcinoma cell lines reduced expression of HSP70 and, to a lesser extent, HSP60. Down modulation of HSPs was not dependent on the presence of the vacuolating cytotoxin (VacA) or the cag pathogenicity island (cag PAI). C57BL/6 mice infected with a human H. pylori strain also demonstrated reduced expression of HSP70, HSP8, and heat shock factor 1 (HSF-1), a transcriptional activator of HSP70. In contrast, the bacterial pathogen, S. Typhimurium up-regulated HSP expression. Since HSPs are thought to function as danger signals during microbial infection, H. pylori down-regulation of HSPs may be a mechanism of immune evasion that promotes chronic infection.
热休克蛋白（HSPs）主要作为分子伴侣为人所知，它们由细胞应激诱导产生，可防止蛋白质聚集并促进蛋白质折叠。最近有证据表明，细胞暴露于微生物病原体也可诱导HSPs产生，进而调节先天性免疫反应和适应性免疫反应。矛盾的是，已发现幽门螺杆菌会降低HSPs的表达。我们试图进一步研究这一现象，并在细胞培养和小鼠模型中研究不同幽门螺杆菌菌株及其公认的毒力因子的作用。幽门螺杆菌与两种胃癌细胞系共培养可降低HSP70的表达，在较小程度上也可降低HSP60的表达。HSPs的下调并不依赖于空泡毒素（VacA）或cag致病岛（cag PAI）的存在。感染人幽门螺杆菌菌株的C57BL/6小鼠也表现出HSP70、HSP8和热休克因子1（HSF-1，HSP70的转录激活因子）的表达降低。相比之下，细菌病原体鼠伤寒沙门氏菌则上调HSP的表达。由于HSPs被认为在微生物感染期间作为危险信号发挥作用，幽门螺杆菌对HSPs的下调可能是一种促进慢性感染的免疫逃避机制。
