UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2020-05-12

Document Type

Article

Disciplines

Biological Phenomena, Cell Phenomena, and Immunity | Immune System Diseases | Immunology and Infectious Disease | Infectious Disease | Macromolecular Substances

Abstract

The inflammasomes control the bioactivity of pro-inflammatory cytokines of the interleukin (IL)-1 family. The inflammasome assembled by NLRP3 has been predominantly studied in homogeneous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets boost the inflammasome capacity of human macrophages and neutrophils and are critical for IL-1 production by monocytes. Platelets license NLRP3 transcription, thereby enhancing ASC oligomerization, caspase-1 activity, and IL-1beta secretion. Platelets influence IL-1beta production in vivo, and blood platelet counts correlate with plasmatic IL-1beta levels in malaria. Furthermore, we reveal an enriched platelet gene signature among the highest-expressed transcripts in IL-1beta-driven autoinflammatory diseases. The platelet effect is independent of cell-to-cell contact, platelet-derived lipid mediators, purines, nucleic acids, and a host of platelet cytokines, and it involves the triggering of calcium-sensing receptors on macrophages. Hence, platelets provide an additional layer of regulation of inflammasomes and IL-1-driven inflammation.

Keywords

ASC, Caspase-1, Cell Death, NLRP3, Pyroptosis, auto-inflammatory diseases, inflammasomes, interleukin-1, malaria, platelets

Rights and Permissions

Copyright 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.celrep.2020.107615

Source

Cell Rep. 2020 May 12;31(6):107615. doi: 10.1016/j.celrep.2020.107615. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

32402278

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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