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

• NLRP3 engaged in the secretion of inflammatory mediators after E. coli treatment. • NLRP3 engaged in the activation of MAPK and NF-κB signaling-pathway. • NLRP3 engaged in caspase1 signaling-pathway activation after E. coli treatment. • NLRP3 contributes to liver damage in mice after E. coli infection. The host Toll-like Receptor-2 (TLR2) and Toll-like Receptor-4 (TLR4) play critical roles in defense against Escherichia coli (E. coli) infection is well-known. The NLR pyrin domain-containing 3 (NLRP3) inflammasome is also an important candidate during the host-recognized pathogen, while the roles of NLRP3 in the host inflammatory response to E. coli infection remains unclear. This study aimed to explore the roles of NLRP3 in regulating the inflammatory response in E. coli infection-induced mice. Our result indicated that compared to wild-type mice, the TLR2-deficient (TLR2-/-), TLR4-deficient (TLR4-/-), and NLRP3-deficient (NLRP3-/-) mice had significant decrease in liver damage after stimulation with Lipopolysaccharide (LPS, 1 μg/mL), Braun lipoprotein (BLP, 1 μg/mL), or infected by WT E. coli (1 × 107 CFU, MOI 5:1). Meanwhile, compared with wild-type mice, the TNF-α and IL-1β production in serum decreased in TLR2-/-, TLR4-/-, and NLRP3-/- mice after LPS, BLP treatment, or WT E. coli infection. In macrophages from NLRP3-/- mice showed significantly reduced secretion of TNF-α and IL-1β in response to stimulation with LPS, BLP, or WT E. coli infection compared with macrophages from wild-type mice. These results indicate that besides TLR2 and TLR4, NLRP3 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. [ABSTRACT FROM AUTHOR]