The role of potassium in inflammasome activation by bacteria.

Abstract

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.

• Authors: Cecilia S Lindestam Arlehamn, Virginie Pétrilli, Olaf Gross, Jürg Tschopp, Tom J Evans
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 14 Pg. 10508-18 (Apr 02 2010) ISSN: 1083-351X [Electronic] United States
• PMID: 20097760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Interleukin-1beta
• Caspase 1
• Potassium

Topics

• Animals
• Bacterial Proteins (metabolism)
• Caspase 1 (metabolism)
• Immunoblotting
• Inflammation (immunology, metabolism)
• Interleukin-1beta (metabolism)
• Mice
• Mice, Inbred C57BL
• Potassium (metabolism)
• Pseudomonas Infections (immunology, metabolism, microbiology)
• Pseudomonas aeruginosa (pathogenicity)
• Salmonella Infections (immunology, metabolism, microbiology)
• Salmonella typhimurium (pathogenicity)