The role of potassium in inflammasome activation by bacteria

Arlehamn, C.S.L., Petrilli, V., Gross, O., Tschopp, J. and Evans, T.J. (2010) The role of potassium in inflammasome activation by bacteria. Journal of Biological Chemistry, 285(14), pp. 10508-10518. (doi: 10.1074/jbc.M109.067298)

Abstract

Many Gram-negative bacteria possess a type III secretion system (TTSS center dot) that can activate the NLRC4 inflammasome, process caspase-1 and lead to secretion of mature IL-1 beta. 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 PA103 Delta U Delta T at concentrations above 90mM, 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.

• Item Type: Articles
• Keywords: Biology, caspase-1 activation, cell-death, cells, death, gene family, identification, immunity, infection, innate immune-responses, ipaf, level, NALP3 inflammasome, pseudomonas-aeruginosa, receptor, reflects, salmonella, scotland, secretion, type III secretion
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Evans, Professor Tom
• Authors: Arlehamn, C.S.L., Petrilli, V., Gross, O., Tschopp, J., and Evans, T.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Biological Chemistry
• Journal Abbr.: J Biol Chem.
• Publisher: American Society for Biochemistry and Molecular Biology, Inc.
• ISSN: 0021-9258
• ISSN (Online): 1083-351X