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

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 & mu;g/mL), Braun lipoprotein (BLP, 1 & mu;g/mL), or infected by WT E. coli (1 x 107 CFU, MOI 5:1). Meanwhile, compared with wild-type mice, the TNF-& alpha; and IL-1 & beta; 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-& alpha; and IL-1 & beta; in response to stimulation with LPS, BLP, or WT E. coli infection compared with macrophages from wildtype 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.

Automated summary

This study investigated the role of NLRP3 in regulating the inflammatory response in E. coli infection-induced mice. The results showed that TLR2-deficient, TLR4-deficient, and NLRP3-deficient mice had reduced liver damage and decreased production of TNF-α and IL-1β compared to wild-type mice. Macrophages from NLRP3-deficient mice also showed reduced secretion of TNF-α and IL-1β in response to stimulation. These findings suggest that NLRP3 plays a critical role in the host inflammatory response to E. coli infection.