Involvement of NLRP3 and NLRC4 Inflammasome in Uropathogenic E. coli Mediated Urinary Tract Infections

Inflammatory response during urinary tract infection (UTI) is mediated by innate immune defense. Nod like receptors (NLRs) have been proposed to work simultaneously beside TLR pathways to mediate pro-inflammatory response and maintain tissue homeostasis. Some reports have showed the involvement of inflammasome during uropathogenic (UPEC) mediated UTI. So we have sought to determine the status of various inflammasomes and their components in UPEC mediated UTI. A total of 186 females experiencing the first episode of UTI were recruited for the study and forty were found to be positive for UPEC (≥10 CFU/ml) in their urine ( = 40). Further, we analyzed the expression of , , , , , , and gene at mRNA and protein level in the blood of UPEC confirmed study subjects through real time qPCR and immunoblotting. Healthy females ( = 40) visiting the OPD for health checkups, family planning advice and subjects undergoing routine medical examinations, were recruited as healthy control subjects. Pro-inflammatory cytokines (IL-6, IL-8, IFN-γ, TNF-α and MCP-1) were measured in the plasma of patients and controls through ELISA. For investigation of the involvement of and inflammasome, studies were performed using co-immunoprecipitation and confocal microscopy. Most of the inflammatory regulators studied (i.e., , and ) were found to be up-regulated at both mRNA and protein levels in the UPEC infected UTI patients. Also, pro-inflammatory cytokines (IL-6, IL-8, IFN-γ, TNF-α, and MCP-1) were found to be up-regulated in the patients group. However, no significant difference was observed in the expression of and genes at both mRNA and protein levels. Further, studies have shown the involvement of NLRC4 inflammasome in UPEC infected THP1 derived macrophages. Involvement of and inflammasomes in UPEC infected UTI is evident from our findings. This is the first report showing levels of inflammasome and its components in UTI patients suggesting a possible role during UPEC mediated UTI. We have also reported the involvement of inflammasome for the first time during UTI infection.