Quorum sensing signal molecules cause renal tissue inflammation through local cytokine responses in experimental UTI caused by Pseudomonas aeruginosa

Quorum sensing (QS) plays a pivotal role in the virulence of Pseudomonas aeruginosa. Urinary tract infections (UTI's) caused by P. aeruginosa leads to tissue destruction and inflammation. Interaction of host immune cells and pathogen at the epithelial surface are regulated by cytokines. Role of virulence factors has been implicated in the induction of renal cytokine responses. However, information regarding the role of QS, an important virulence factor of P. aeruginosa, is lacking. This study examined role of QS signal molecules for their ability to induce pro and anti-inflammatory renal cytokines and inflammation in experimental UTI. For this, both standard parent P. aeruginosa strain (PAO1) capable of producing QS signal molecules and its isogenic single and double mutant strains lacking this ability were used. Mice infected with QS producer strain PAO1, evoked significant renal tissue inflammation and cytokine response with high neutrophil migration and AHL production in vivo. Mild inflammation, low level of renal cytokines and other factors were observed in mice infected with QS single and double mutant strains. These results provide first evidence regarding the role of QS signal molecules and point towards the importance of AHLs in induction of renal cytokines and tissue inflammatory responses.