Loss of NLRP3 increases bacterial cystitis via IRAKM.

Abstract

BackgroundWe attempted to characterize the molecular mechanisms that underpin urinary tract infections using a mouse model of cystitis induced by bacterial infection in a background of NOD-, LRR- and PYD domains-containing protein (NLRP3) deficiency.MethodsMale NLRP3 knockout (NLRP3−/−) and control mice (12 weeks old) were intraurethrally inoculated with 2×108 Escherichia coli (E. coli) and euthanized 1, 3, and 7 days later to assess the degree of bladder infection. Immunohistochemical detection of NLRP3 and interleukin-1 receptor-associated kinase M (IRAKM) was performed. Quantitative PCR analysis was performed to analyze the expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α.ResultsBladder infection was observed in control mice 1 day after inoculation with E. coli. The infection had disappeared by day 7. IL-1β and TNF-α levels were lower 1 day after injection but higher on days 3 and 7 in the NLRP3−/− group compared with the control mice (P<0.05). Expression of NLRP3 and IRAKM in wild-type (WT) group were significantly decreased 1 day post infection, and by day 7 were increased back to similar level on day 0. On the contrary, in the NLRP3−/− group, IRAKM was significantly lower than WT mice on day 0 and were significantly decreased by day 7.ConclusionsDeficiency of NLRP3 expression in NLRP3−/− mice contributes to the pathogenesis of chronic inflammation associated with cystitis through IRAKM.