Platelets Fuel the Inflammasome Activation of Innate Immune Cells
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
Biological Phenomena, Cell Phenomena, and Immunity
Immune System Diseases
Immunology and Infectious Disease
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AbstractThe 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.
Cell Rep. 2020 May 12;31(6):107615. doi: 10.1016/j.celrep.2020.107615. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41457
Full author list omitted for brevity. For the full list of authors, see article.
RightsCopyright 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/).
Except where otherwise noted, this item's license is described as 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/).