The role of potassium in inflammasome activation by bacteria.
Many Gram-negative bacteria possess a type III secretion system (TTSS( paragraph sign)) that can activate the NLRC4 inflammasome, process caspase-1 and lead to secretion of mature IL-1beta. 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 PA103DeltaUDeltaT 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.
Arlehamn
Cecilia S Lindestam
CS
Division of Immunology, Infection, and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
Pétrilli
Virginie
V
Gross
Olaf
O
Tschopp
Jürg
J
Evans
Tom J
TJ
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011188:Potassium / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D012480:Salmonella Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000472:pathogenicity*
D001426:Bacterial Proteins; D053583:Interleukin-1beta; D020170:Caspase 1; D011188:Potassium