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NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production?

Abstract

The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that activates caspase 1, leading to the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. The NLRP3 inflammasome is activated by a wide range of danger signals that derive not only from microorganisms but also from metabolic dysregulation. It is unclear how these highly varied stress signals can be detected by a single inflammasome. In this Opinion article, we review the different signalling pathways that have been proposed to engage the NLRP3 inflammasome and suggest a model in which one of the crucial elements for NLRP3 activation is the generation of reactive oxygen species (ROS).

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Figure 1: Mechanism of NLRP3 inflammasome complex formation.
Figure 2: The channel model of NLRP3 inflammasome activation.
Figure 3: The lysosome rupture model of NLRP3 inflammasome activation.
Figure 4: The reactive oxygen species model of NLRP3 inflammasome activation.

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Acknowledgements

J.T. is supported by grants from the Swiss National Science Foundation, by EU grants Mugen, Hermione, Apo-Sys and Apo-Train and by the Institute of Arthritis Research. K.S. is supported by a CJ Martin Fellowship from the Australian National Health and Medical Research Council (ID 490993).

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Tschopp, J., Schroder, K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production?. Nat Rev Immunol 10, 210–215 (2010). https://doi.org/10.1038/nri2725

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