The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Cytosolic Double-Stranded RNA Activates the NLRP3 Inflammasome via MAVS-Induced Membrane Permeabilization and K+ Efflux
Open accessAbstract
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.
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Cites
A role for mitochondria in nlrp3 inflammasome activation
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Activation and regulation of the inflammasomes
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Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
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IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
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Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis
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Cited by
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884
The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation
Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133328 · Cited by 3,539
Mechanism and Regulation of NLRP3 Inflammasome Activation
He, Y., Hara, H., & Núñez, G. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.09.002 · Cited by 2,759
Self-citationMitochondrial control of inflammation
Marchi, S., Guilbaud, E., Tait, S. W. G., Yamazaki, T., & Galluzzi, L. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00760-x · Cited by 1,027
An update on the regulatory mechanisms of NLRP3 inflammasome activation
Paik, S., Kim, J. K., Silwal, P., Sasakawa, C., & Jo, E.-K. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00670-3 · Cited by 892
Metadata
- Authors
- Franchi, L., Eigenbrod, T., Muñoz-Planillo, R., Ozkurede, U., Kim, Y.-G., Chakrabarti, A., Gale, M., Silverman, R. H., Colonna, M., Akira, S., & Núñez, G.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10
- Volume
- 193
- Issue
- 8
- Pages
- 4214-4222
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1804579058
- Cited by
- 183
- References
- 17
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- green
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- Franchi, L., Eigenbrod, T., Muñoz-Planillo, R., Ozkurede, U., Kim, Y.-G., Chakrabarti, A., Gale, M., Silverman, R. H., Colonna, M., Akira, S., & Núñez, G. (2014). Cytosolic Double-Stranded RNA Activates the NLRP3 Inflammasome via MAVS-Induced Membrane Permeabilization and K+ Efflux. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1400582
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