Cytosolic double-stranded RNA activates the NLRP3 inflammasome via MAVS-induced membrane permeabilization and K+ efflux

• Verfasst von: Franchi, Luigi [VerfasserIn]
• Verfasst von: Eigenbrod, Tatjana [VerfasserIn]
• Verfasst von: Muñoz-Planillo, Raúl [VerfasserIn]
• Verfasst von: Ozkurede, Ulas [VerfasserIn]
• Verfasst von: Kim, Yun-Gi [VerfasserIn]
• Verfasst von: Chakrabarti, Arindam [VerfasserIn]
• Verfasst von: Gale, Michael [VerfasserIn]
• Verfasst von: Silverman, Robert H. [VerfasserIn]
• Verfasst von: Colonna, Marco [VerfasserIn]
• Verfasst von: Akira, Shizuo [VerfasserIn]
• Verfasst von: Núñez, Gabriel [VerfasserIn]
• Titel: Cytosolic double-stranded RNA activates the NLRP3 inflammasome via MAVS-induced membrane permeabilization and K+ efflux
• Verf.angabe: Luigi Franchi, Tatjana Eigenbrod, Raúl Muñoz-Planillo, Ulas Ozkurede, Yun-Gi Kim, Arindam Chakrabarti, Michael Gale, Robert H. Silverman, Marco Colonna, Shizuo Akira, and Gabriel Núñez
• E-Jahr: 2014
• Jahr: 15 September 2014
• Umfang: 9 S.
• Fussnoten: Gesehen am 08.07.2020
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2014
• Band/Heft Quelle: 193(2014), 8, Seite 4214-4222
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.1400582
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1713903598

Abstract

The nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (Nlrp3) inflammasome plays an important role in inflammation by controlling the maturation and secretion of the cytokines IL-1β and IL-18 in response to multiple stimuli including pore-forming toxins, particulate matter, and ATP. Although the pathways activated by the latter stimuli lead to a decrease in intracellular K+ concentration, which is required for inflammasome activation, the mechanism by which microbial RNA activates Nlrp3, remains poorly understood. In this study, we found that cytosolic poly(I:C), but not total RNA from healthy macrophages, macrophages undergoing pyroptosis, or mitochondrial RNA, induces caspase-1 activation and IL-1β release through the Nlrp3 inflammasome. Experiments with macrophages deficient in Tlr3, Myd88, or Trif, indicate that poly(I:C) induces Nlrp3 activation independently of TLR signaling. Further analyses revealed that the cytosolic sensors Rig-I and melanoma differentiation-associated gene 5 act redundantly via the common adaptor mitochondrial antiviral signaling (Mavs) to induce Nlrp3 activation in response to poly(I:C), but not ATP or nigericin. Mechanistically, Mavs triggered membrane permeabilization and K+ efflux independently of the inflammasome which were required for poly(I:C)-induced Nlrp3 activation. We conclude that poly (I:C) activates the inflammasome through an Mavs-dependent surveillance pathway that converges into a common K+ lowering step in the cytosol that is essential for the induction of Nlrp3 activation.