Nlrc4/Ipaf/CLAN/CARD12: more than a flagellin sensor

Int J Biochem Cell Biol. 2010 Jun;42(6):789-91. doi: 10.1016/j.biocel.2010.01.003. Epub 2010 Jan 11.

Abstract

Nlrc4 is a member of the Nod-like receptors (NLRs), a family of cytosolic receptors involved in sensing bacterial molecules. NLRs are a group of proteins containing spans of leucine-rich repeats that senses bacterial factors within the eukaryotic cytosol. The recognition of bacterial factors provokes the formation of the inflammasome complex which includes specific NLRs. The inflammasome is responsible for caspase-1 activation which leads to the cleavage and maturation of inflammatory cytokines such as IL-1beta and IL-18. Nlrc4 was considered to be a devoted flagellin sensor in eukaryotic cells. However, studies using a variety of pathogens such as Salmonella, Legionella, Shigella and Pseudomonas at high bacterial burdens revealed that Nlrc4 can mediate caspase-1 activation independent of bacterial flagellin. On the other hand, new reports showed that Nlrc4 can restrict bacterial infection independently of caspase-1. Therefore, Nlrc4 maybe involved in sensing more than one bacterial molecule and may participate in several immune complexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacterial Infections / immunology*
  • Bacterial Infections / metabolism
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / immunology
  • CARD Signaling Adaptor Proteins / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / immunology
  • Calcium-Binding Proteins / metabolism*
  • Caspase 1 / metabolism
  • Flagellin / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Mucocutaneous Lymph Node Syndrome / genetics
  • Mucocutaneous Lymph Node Syndrome / immunology
  • Mucocutaneous Lymph Node Syndrome / metabolism
  • Multiprotein Complexes / immunology*

Substances

  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins
  • Interleukin-18
  • Interleukin-1beta
  • Multiprotein Complexes
  • NLRC4 protein, human
  • Flagellin
  • Caspase 1