Department of Medicine, Division of Infectious Diseases and Immunology
Cell Biology | Immunology and Infectious Disease
Infectious organisms and damage of cells can activate inflammasomes, which mediate tissue inflammation and adaptive immunity. These mechanisms evolved to curb the spread of microbes and to induce repair of the damaged tissue. Chronic activation of inflammasomes, however, contributes to non-resolving inflammatory responses that lead to immuno-pathologies. Inflammasome-activated cells undergo an inflammatory cell death associated with the release of potent pro-inflammatory cytokines and poorly characterized extracellular vesicles (EVs). Since inflammasome-induced EVs could signal inflammasome pathway activation in patients with chronic inflammation and modulate bystander cell activation, we performed a systems analysis of the ribonucleic acid (RNA) content and function of two EV classes. We show that EVs released from inflammasome-activated macrophages carry a specific RNA signature and contain interferon beta (IFNbeta). EV-associated IFNbeta induces an interferon signature in bystander cells and results in dampening of NLRP3 inflammasome responses. EVs could, therefore, serve as biomarkers for inflammasome activation and act to prevent systemic hyper-inflammatory states by restricting NLRP3 activation in bystander cells.
cell communication, extracellular vesicle, inflammasome, inflammation, interferon β, nucleotide‐binding oligomerization domain (NOD)‐containing protein with a pyrin domain (NLRP3), pyroptosis
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Copyright © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
DOI of Published Version
Budden CF, Gearing LJ, Kaiser R, Standke L, Hertzog PJ, Latz E. Inflammasome-induced extracellular vesicles harbour distinct RNA signatures and alter bystander macrophage responses. J Extracell Vesicles. 2021 Aug;10(10):e12127. doi: 10.1002/jev2.12127. Epub 2021 Aug 2. PMID: 34377374; PMCID: PMC8329986. Link to article on publisher's site
Journal of extracellular vesicles
Budden CF, Gearing LJ, Kaiser R, Standke L, Hertzog PJ, Latz E. (2021). Inflammasome-induced extracellular vesicles harbour distinct RNA signatures and alter bystander macrophage responses. Open Access Publications by UMass Chan Authors. https://doi.org/10.1002/jev2.12127. Retrieved from https://escholarship.umassmed.edu/oapubs/4895
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.