NLRP3 mediated dysfunction of mitochondria leads to cell death in CFT073 stimulated macrophages

Urinary tract infections (UTIs) are commonly caused by uropathogenic E coli (UPEC), which uses different mechanisms to invade and damage hosts. NLRP3 inflammasome activation is a double-edged sword, although beneficial in the clearance of dysfunctional cells or pathogens but results severe pathologies, if unchecked. plays critical role UPEC-mediated inflammatory cell death during UPEC infection, though effects its not clearly understood yet. Inflammatory response usually involves Signal-I (MyD88, TRIF NF-κB signalling) Signal-II (Inflammasome oligomerization) induced pathogen-associated molecular patterns infection. We observed that proIL-1β mature IL-1β remained unchanged on inhibition MyD88 TRIF-dependent signalling CFT073-insulted THP-1m. However, pathway resulted concomitant reduction both pro- cleaved forms cellular extracts there was no change IL-1 β secretion. Interestingly, completely abolished maturation release form IL-1β. Additionally, NLRP3-mediated mitochondrial dysfunction (increased mito-ROS hyperpolarization) resulting THP-1m, rescued upon activation. Therefore, we have concluded signal-I (other than TRIF), while major signal-II for induction response. Further, this study signifies importance CFT073-induced macrophages, could be through