Mitochondrial damage helps activate inflammation by Pseudomonas aeruginosa and is reduced by cellular cleanup

Infection with Pseudomonas aeruginosa activates the NLRC4 inflammasome through mitochondrial damage and mitochondrial DNA release.

• Pathogenic bacteria use a specialized secretion system to activate the NLRC4 inflammasome.
• Mitochondrial damage during infection leads to increased production of reactive oxygen species and release of mitochondrial DNA.
• Inhibition of mitochondrial reactive oxygen release or degradation of mitochondrial DNA prevents NLRC4 inflammasome activation.
• Macrophages without mitochondria do not activate the NLRC4 inflammasome upon infection.
• Autophagy reduces NLRC4 inflammasome activation by removing damaged mitochondria.
• Mitochondrial DNA can activate the NLRC4 inflammasome directly, with oxidation enhancing this activation.

Simplified