The role of potassium in inflammasome activation by bacteria.
The role of potassium in inflammasome activation by bacteria.
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DOI：
10.1074/jbc.m109.067298
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发表时间：
2010-04-02
期刊：
影响因子：
--
通讯作者：
Evans TJ
中科院分区：
文献类型：
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作者：
Arlehamn CS;Pétrilli V;Gross O;Tschopp J;Evans TJ
许多革兰氏阴性菌具有III型分泌系统（TTSS <$），其可以激活NLRC 4炎性体，加工caspase-1并导致成熟IL-1β的分泌。这取决于细胞内鞭毛蛋白的存在。以前的报道表明，这种激活不依赖于细胞外K+，并且与NLRP 3炎性体的激活相反，不伴随K+从细胞中的泄漏。然而，铜绿假单胞菌的非鞭毛型菌株能够激活NLRC 4，这表明通过TTSS装置在细胞膜中形成孔可能足以激活炎性小体。因此，我们着手确定细胞外K+是否影响铜绿假单胞菌炎性小体激活。我们发现，在高于90 mM的浓度下，提高细胞外K+可阻止无鞭毛铜绿假单胞菌菌株PA 103 ΔUΔT激活TTSS NLRC 4，高于报道的抑制NLRP 3激活的浓度。感染伴随着从少数细胞的K+流出，如使用K+敏感的荧光团PBFI所确定的，但没有形成渗漏孔。我们获得了完全相同的结果，感染鼠伤寒沙门氏菌，以前描述为独立的细胞外K+。因此，升高的细胞外K+对NLRC 4活化的抑制作用反映了这种炎性体组分以及NLRP 3所述的细胞内K+降低的要求。
Many Gram-negative bacteria possess a type III secretion system (TTSS¶) that can activate the NLRC4 inflammasome, process caspase-1 and lead to secretion of mature IL-1β. This is dependent on the presence of intracellular flagellin. Previous reports have suggested that this activation is independent of extracellular K+ and not accompanied by leakage of K+ from the cell, in contrast to activation of the NLRP3 inflammasome. However, non-flagellated strains of Pseudomonas aeruginosa are able to activate NLRC4, suggesting that formation of a pore in the cell membrane by the TTSS apparatus may be sufficient for inflammasome activation. Thus, we set out to determine if extracellular K+ influenced P. aeruginosa inflammasome activation. We found that raising extracellular K+ prevented TTSS NLRC4 activation by the non-flagellated P. aeruginosa strain PA103ΔUΔT at concentrations above 90 mm, higher than those reported to inhibit NLRP3 activation. Infection was accompanied by efflux of K+ from a minority of cells as determined using the K+-sensitive fluorophore PBFI, but no formation of a leaky pore. We obtained exactly the same results following infection with Salmonella typhimurium, previously described as independent of extracellular K+. The inhibitory effect of raised extracellular K+ on NLRC4 activation thus reflects a requirement for a decrease in intracellular K+ for this inflammasome component as well as that described for NLRP3.