Pyrin Domain (PYD)-containing Inflammasome in Innate Immunity

Inflammasome is a cytosolic multiprotein complex to activate caspase-1 leading to the subsequent processing of inactive pro-interleukin-1-beta (Pro-IL-1β) into its active interleukin-1 beta (IL-1β) in response to pathogen-or dangerassociated 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-1β-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.