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Gene Review

Nlrc4  -  NLR family, CARD domain containing 4

Mus musculus

Synonyms: 9530011P19Rik, CLAN, CLAN1, CLANA, CLANB, ...
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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].


  1. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. Franchi, L., Amer, A., Body-Malapel, M., Kanneganti, T.D., Ozören, N., Jagirdar, R., Inohara, N., Vandenabeele, P., Bertin, J., Coyle, A., Grant, E.P., Núñez, G. Nat. Immunol. (2006) [Pubmed]
  2. Regulation of Legionella Phagosome Maturation and Infection through Flagellin and Host Ipaf. Amer, A., Franchi, L., Kanneganti, T.D., Body-Malapel, M., Oz??ren, N., Brady, G., Meshinchi, S., Jagirdar, R., Gewirtz, A., Akira, S., N????ez, G. J. Biol. Chem. (2006) [Pubmed]
  3. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Miao, E.A., Alpuche-Aranda, C.M., Dors, M., Clark, A.E., Bader, M.W., Miller, S.I., Aderem, A. Nat. Immunol. (2006) [Pubmed]
  4. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Mariathasan, S., Newton, K., Monack, D.M., Vucic, D., French, D.M., Lee, W.P., Roose-Girma, M., Erickson, S., Dixit, V.M. Nature (2004) [Pubmed]
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