Uropathogenic Escherichia coli strain CFT073 disrupts NLRP3 inflammasome activation

J Clin Invest. 2016 Jul 1;126(7):2425-36. doi: 10.1172/JCI81916. Epub 2016 May 23.


Successful bacterial pathogens produce an array of virulence factors that allow subversion of the immune system and persistence within the host. For example, uropathogenic Escherichia coli strains, such as CFT073, express Toll/IL-1 receptor-containing (TIR-containing) protein C (TcpC), which impairs TLR signaling, thereby suppressing innate immunity in the urinary tract and enhancing persistence in the kidneys. Here, we have reported that TcpC also reduces secretion of IL-1β by directly interacting with the NACHT leucin-rich repeat PYD protein 3 (NLRP3) inflammasome, which is crucial for recognition of pathogens within the cytosol. At a low MOI, IL-1β secretion was minimal in CFT073-infected macrophages; however, IL-1β release was markedly increased in macrophages infected with CFT073 lacking tcpC. Induction of IL-1β secretion by CFT073 and tcpC-deficient CFT073 required the NLRP3 inflammasome. TcpC attenuated activation of the NLRP3 inflammasome by binding both NLRP3 and caspase-1 and thereby preventing processing and activation of caspase-1. Moreover, in a murine urinary tract infection model, CFT073 infection rapidly induced expression of the NLRP3 inflammasome in the bladder mucosa; however, the presence of TcpC in WT CFT073 reduced IL-1β levels in the urine of infected mice. Together, these findings illustrate how uropathogenic E. coli use the multifunctional virulence factor TcpC to attenuate innate immune responses in the urinary tract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Caspase 1 / metabolism
  • Cytosol / metabolism
  • Escherichia coli Proteins / metabolism
  • Female
  • HEK293 Cells
  • Humans
  • Immunity, Innate
  • Inflammasomes / metabolism*
  • Interleukin-1beta / metabolism
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Protein Domains
  • Urinary Tract Infections / microbiology*
  • Uropathogenic Escherichia coli*
  • Virulence Factors / metabolism


  • Escherichia coli Proteins
  • IL1B protein, human
  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Nlrp3 protein, mouse
  • TcpC protein, E coli
  • Virulence Factors
  • Caspase 1