J Bacteriol Virol.  2011 Sep;41(3):133-146. 10.4167/jbv.2011.41.3.133.

Pyrin Domain (PYD)-containing Inflammasome in Innate Immunity

• Hong S
• Park S
• Yu JW

• KMID: 1449888
• DOI: http://doi.org/10.4167/jbv.2011.41.3.133

Abstract

Inflammasome is a cytosolic multiprotein complex to activate caspase-1 leading to the subsequent processing of inactive pro-interleukin-1-beta (Pro-IL-1beta) into its active interleukin-1 beta (IL-1beta) in response to pathogen- or danger-associated molecular pattern. In recent years, a huge progress has been made to identify inflammasome component as a molecular platform to recruit and activate caspase-1. Nucleotide-binding oligomerization domain-like receptor (NLR) family proteins such as NLRP1, NLRP3 or interleukin-1beta-converting enzyme (ICE)-protease activating factor (IPAF) have been first characterized to form inflammasome complex to induce caspase-1 activation. More recently, non-NLR type, pyrin-domain (PYD)-containing proteins such as pyrin or absent in melanoma2 (AIM2) were also proposed to form caspase-1-activating inflammasome machinery with apoptosis-associated speck-like protein containing a CARD (ASC), an essential adaptor molecule. Inflammasome pathways were shown to be crucial for protecting host organisms against diverse pathogen infections, but accumulating evidences also suggest that excessive activation of inflammasome/caspase-1 might be related to the pathogenesis of inflammation-related diseases. Indeed, mutations in NLRP3 or pyrin are closely associated with autoinflammatory diseases such as familial Mediterranean fever (FMF) syndrome or Muckle-Wells syndrome (MWS), indicating that the regulation of caspase-1 activity by inflammasome is a central process in these hereditary inflammatory disorders. Here, recent advances on the molecular mechanism of caspase-1 activation by PYD-containing inflammasomes are summarized and discussed.

Keyword

Inflammasome; Caspase-1; Interleukin-1-beta (IL-1beta); Pyrin-domain (PYD); NLR; Autoinflammatory disease

MeSH Terms

Cryopyrin-Associated Periodic Syndromes
Cytoskeletal Proteins
Cytosol
Familial Mediterranean Fever
Humans
Immunity, Innate
Inflammasomes
Interleukin-1beta
Proteins
Cytoskeletal Proteins
Inflammasomes
Interleukin-1beta
Proteins

Figure

• 

  Figure 1. Pattern-recognition receptor (PRR) signaling pathways. Three classes of PRR families, such as TLRs, RLRs and NLRs, sense microbial products or endogenous danger signals to trigger downstream signaling pathways, resulting in the production of type I IFN, proinflammatory cytokines and the activation of caspase-1.

• 

  Figure 2. PYD-containing inflammasome pathways. Inactive PYD-containing inflammasome components are activated by sensing diverse microbial infection or danger signals (NLRP3), cytoplasmic dsDNA (AIM2) and autoinflammatory disease-associated PSTPIP1 mutant (pyrin) to trigger the formation of ASC pyroptosome, resulting in the activation of caspase-1.

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