UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2021-08-02

Document Type

Article

Disciplines

Cell Biology | Immunology and Infectious Disease

Abstract

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.

Keywords

cell communication, extracellular vesicle, inflammasome, inflammation, interferon β, nucleotide‐binding oligomerization domain (NOD)‐containing protein with a pyrin domain (NLRP3), pyroptosis

Rights and Permissions

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

10.1002/jev2.12127

Source

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/Book/Conference Title

Journal of extracellular vesicles

Related Resources

Link to Article in PubMed

PubMed ID

34377374

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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