Besides TLR2 and TLR4, NLRP3 is also involved in regulating Escherichia coli infection-induced inflammatory responses in mice

Abstract The host TLR2 and TLR4 play critical roles in defense against Escherichia coli (E. coli) infection. The NLRP3 inflammasome is the most thoroughly characterized and responds to numerous physically and chemically diverse stimuli. However, the underlying molecular mechanism of TLR2, TLR4 and NLRP3 in the host inflammatory response to E. coli infection remains unclear. This study aimed to explore the roles of TLR2, TLR4 and NLRP3 in regulating the inflammatory response in E. coli infection-induced mice. Our result indicated that macrophages from NLRP3-deficient mice showed significantly reduced secretion of TNF-α and IL-1β and cyclooxygenase-2 (COX-2) expression in response to stimulation with lipopolysaccharide (LPS), braun lipoprotein (BLP), or WT E. coli compared with macrophages from wild-type mice. In addition, TNF-α and IL-1β production in mouse serum after stimulation agreed with the macrophage data. Liver damage in TLR2-deficient, TLR4-deficient, and NLRP3-deficient mice significantly decreased compared to wild-type mice after stimulation with LPS, BLP, or WT E. coli. These results indicate that besides TLR2 and TLR4, NLRP3 is also plays a critical role in host inflammatory responses to defense against E. coli infection, and might provide a therapeutic target in combating disease with bacterium infection.