Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome

PLoS Pathog. 2012;8(3):e1002638. doi: 10.1371/journal.ppat.1002638. Epub 2012 Mar 29.


NOD-like receptor (NLR) proteins (Nlrps) are cytosolic sensors responsible for detection of pathogen and danger-associated molecular patterns through unknown mechanisms. Their activation in response to a wide range of intracellular danger signals leads to formation of the inflammasome, caspase-1 activation, rapid programmed cell death (pyroptosis) and maturation of IL-1β and IL-18. Anthrax lethal toxin (LT) induces the caspase-1-dependent pyroptosis of mouse and rat macrophages isolated from certain inbred rodent strains through activation of the NOD-like receptor (NLR) Nlrp1 inflammasome. Here we show that LT cleaves rat Nlrp1 and this cleavage is required for toxin-induced inflammasome activation, IL-1 β release, and macrophage pyroptosis. These results identify both a previously unrecognized mechanism of activation of an NLR and a new, physiologically relevant protein substrate of LT.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, Bacterial / pharmacology*
  • Bacterial Toxins / pharmacology*
  • CHO Cells
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • Inflammasomes / biosynthesis
  • Inflammasomes / drug effects*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Rats, Inbred Lew


  • Antigens, Bacterial
  • Bacterial Toxins
  • Inflammasomes
  • Nerve Tissue Proteins
  • Nlrp1a protein, rat
  • anthrax toxin