Disease relevance of Nlrc4

• Ipaf, a cytosolic pattern-recognition receptor in the family of nucleotide-binding oligomerization domain-leucine-rich repeat proteins, is critical in such a response to salmonella infection, but the mechanism of how Ipaf is activated by the bacterium remains poorly understood [1].
• However, the mechanism by which Ipaf restricts Legionella replication is not well understood [2].

High impact information on Nlrc4

• Thus, detection of flagellin through Ipaf induces caspase-1 activation independently of Toll-like receptor 5 in salmonella-infected and lipopolysaccharide-tolerized macrophages [1].
• Stimulation of the Ipaf pathway in macrophages after infection required a functional salmonella pathogenicity island 1 type III secretion system but not the flagellar type III secretion system; furthermore, Ipaf activation could be recapitulated by the introduction of purified flagellin directly into the cytoplasm [3].
• Delivery of flagellin to the macrophage cytosol induced Ipaf-dependent activation of caspase-1 that was independent of Toll-like receptor 5, required for recognition of extracellular flagellin [1].
• The regulation of phagosome maturation by Ipaf occurred within 2 h after infection and was independent of macrophage cell death [2].
• Here we show the impact of ASC-, Ipaf- or RIP2-deficiency on inflammasome function [4].

Anatomical context of Nlrc4

• Unexpectedly, Ipaf-deficient macrophages activated caspase-1 in response to TLR plus ATP stimulation but not S. typhimurium [4].
• In the absence of Ipaf or caspase-1 activation, the LCP acquired endoplasmic reticulum-derived vesicles, avoided fusion with the lysosome, and allowed Legionella replication [2].

Other interactions of Nlrc4

• Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf [4].

References