An Update on PYRIN Domain-Containing Pattern Recognition Receptors: From Immunity to Pathology

Abstract

Cytosolic pattern recognition receptors (PRRs) sense a wide range of endogenous danger-associated molecular patterns as well as exogenous pathogen-associated molecular patterns. In particular, Nod-like receptors containing a pyrin domain (PYD), called NLRPs, and AIM2-like receptors (ALRs) have been shown to play a critical role in host defense by facilitating clearance of pathogens and maintaining a healthy gut microflora. NLRPs and ALRs both encode a PYD, which is crucial for relaying signals that result in an efficient innate immune response through activation of several key innate immune signaling pathways. However, mutations in these PRRs have been linked to the development of auto-inflammatory and autoimmune diseases. In addition, they have been implicated in metabolic diseases. In this review, we summarize the function of PYD-containing NLRPs and ALRs and address their contribution to innate immunity, host defense, and immune-linked diseases.

DAMPs as mediators of sterile inflammation in aging-related pathologies

“…ROS generation is frequently accompanied by K + efflux (Kowaltowski et al, 2009), although the mechanism for this remains unclear. The involvement of mitochondria in NLRP3 activation remains controversial (Ratsimandresy et al, 2013) despite several examples for DAMP-induced NLRP3 inflammasome activation (Tschopp and Schroder, 2010). Activation of the NLRP3 inflammasome by asbestos and silica has been associated with the production of ROS.…”

“…Ion fluxes also play a role in NLRP3 inflammasome activation, such as K + efflux via ATP activation of its receptor P2X7 and calcium influx via multiple receptors. Mitochondrial-generated ROS also has been suggested to influence NLRP3 activation (Ratsimandresy et al, 2013). The mitochondria have been associated with the creation of ROS as a byproduct of stressors such as hypoxia, acidosis and membrane damage (Rajamäki et al, 2013).…”

Mangiferin Attenuate Sepsis-Induced Acute Kidney Injury via Antioxidant and Anti-Inflammatory Effects

“…Inflammasomes was thought to have a unique ability to integrate a myriad of signals from pathogen- and damage-associated molecular patterns into a proinflammatory response [36]. As the most extensively investigated of the inflammasomes identified, activation of the NLRP3 inflammasome can be achieved by a wide range of structurally dissimilar agonists, including pathogens, pore-forming toxins, environmental irritants, and endogenous damage-associated molecular patterns [37]. Our study found that NLRP3 activation is involved in the pathogenesis of LPS-induced PRTC cells' apoptosis and CLP-induced sepsis.…”

DNA vaccine-mediated innate immune response triggered by PRRs in teleosts

“…In mammals, the AIM2-like receptor (ALR inflammasome) and DDX41 [DEAD/H helicase (DDX) protein] act as cytosolic DNA sensors [95,113]. ALR is a pyrin domaincontaining PRR that forms an inflammasome protein complex with an ASC adaptor to recognize viral and bacterial DNAs [113].…”

“…ALR is a pyrin domaincontaining PRR that forms an inflammasome protein complex with an ASC adaptor to recognize viral and bacterial DNAs [113]. However, no counterparts of the AIM2 gene have been found in any fish species.…”