This Research Topic is the second volume of the “Molecular and Cellular Basis for NLRP3 Sensing of Infectious and Sterile Stimuli” Community Series. Please see the first volume
here.
Elaboration of the proinflammatory cytokines IL-1beta and IL-18 which underpin both protective and pathologic inflammatory responses, relies on activation of caspase-1 by multiprotein complexes called inflammasomes. Inflammasome formation upon specific challenges requires sensor or pattern-recognition receptor (PRR) proteins that respond in a stimulus-restricted fashion to drive caspase-1 activity. While some inflammasome PRRs are restricted to specific stimulating ligands (e.g., dsDNA or flagellin), the NLRP3 inflammasome is activated in response to a wide variety of infectious and sterile agonists. Accordingly, NLRP3 is critical for innate resistance to various infections, important for T-dependent antibody responses, and has been established or implicated in the pathogenesis of numerous inflammatory diseases. How multiple stimuli drive NLRP3 inflammasome activation is not understood, but several fundamental activation models have been proposed. However, despite supporting evidence, contradictory observations are well-known and none of the models provide a clear or completely satisfactory unifying mechanism. The molecular details of NLRP3 inflammasome activation are also poorly understood.
This Research Topic aims at addressing the cellular and molecular processes leading to NLRP3 inflammasome activation with specific emphasis on furthering our understanding of agonist-mediated activation of NLRP3. Of particular interest are the molecular mechanisms by which NLRP3 is triggered to assemble its inflammasome, whether these mechanisms can be generalized to explain the response to all (or groups) of known stimuli or are agonist-specific, the molecular mediators of these processes, and which structural features and post-translational modifications of NLRP3 are involved.
We welcome the submission of Original Research articles, Reviews, Mini-Reviews, and Perspectives focusing on the following sub-topics:
• Refinements or exceptions to the known NLRP3 activation pathways
• Analyses of shared or distinct signaling pathways leading to NLRP3 inflammasome activity
• Analyses of direct or indirect ligand/agonist interaction with NLRP3 or its binding partners
• Analyses of post-translational modifications regulating NLRP3 activation in response to specific ligands
• The molecular regulation of NLRP3 interactions leading to inflammasome assembly/activation
• Comparisons of infectious (PAMP) with sterile (DAMP) stimuli in the above contexts are of particular interest
This Research Topic is the second volume of the “Molecular and Cellular Basis for NLRP3 Sensing of Infectious and Sterile Stimuli” Community Series. Please see the first volume
here.
Elaboration of the proinflammatory cytokines IL-1beta and IL-18 which underpin both protective and pathologic inflammatory responses, relies on activation of caspase-1 by multiprotein complexes called inflammasomes. Inflammasome formation upon specific challenges requires sensor or pattern-recognition receptor (PRR) proteins that respond in a stimulus-restricted fashion to drive caspase-1 activity. While some inflammasome PRRs are restricted to specific stimulating ligands (e.g., dsDNA or flagellin), the NLRP3 inflammasome is activated in response to a wide variety of infectious and sterile agonists. Accordingly, NLRP3 is critical for innate resistance to various infections, important for T-dependent antibody responses, and has been established or implicated in the pathogenesis of numerous inflammatory diseases. How multiple stimuli drive NLRP3 inflammasome activation is not understood, but several fundamental activation models have been proposed. However, despite supporting evidence, contradictory observations are well-known and none of the models provide a clear or completely satisfactory unifying mechanism. The molecular details of NLRP3 inflammasome activation are also poorly understood.
This Research Topic aims at addressing the cellular and molecular processes leading to NLRP3 inflammasome activation with specific emphasis on furthering our understanding of agonist-mediated activation of NLRP3. Of particular interest are the molecular mechanisms by which NLRP3 is triggered to assemble its inflammasome, whether these mechanisms can be generalized to explain the response to all (or groups) of known stimuli or are agonist-specific, the molecular mediators of these processes, and which structural features and post-translational modifications of NLRP3 are involved.
We welcome the submission of Original Research articles, Reviews, Mini-Reviews, and Perspectives focusing on the following sub-topics:
• Refinements or exceptions to the known NLRP3 activation pathways
• Analyses of shared or distinct signaling pathways leading to NLRP3 inflammasome activity
• Analyses of direct or indirect ligand/agonist interaction with NLRP3 or its binding partners
• Analyses of post-translational modifications regulating NLRP3 activation in response to specific ligands
• The molecular regulation of NLRP3 interactions leading to inflammasome assembly/activation
• Comparisons of infectious (PAMP) with sterile (DAMP) stimuli in the above contexts are of particular interest
