Department of Medicine, Division of Infectious Diseases and Immunology
Biological Phenomena, Cell Phenomena, and Immunity | Immune System Diseases | Immunology and Infectious Disease | Infectious Disease | Macromolecular Substances
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.
ASC, Caspase-1, Cell Death, NLRP3, Pyroptosis, auto-inflammatory diseases, inflammasomes, interleukin-1, malaria, platelets
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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
Cell Rep. 2020 May 12;31(6):107615. doi: 10.1016/j.celrep.2020.107615. Link to article on publisher's site
Rolfes V, Ribeiro LS, Latz E, Arditi M, Franklin BS. (2020). Platelets Fuel the Inflammasome Activation of Innate Immune Cells. Open Access Articles. https://doi.org/10.1016/j.celrep.2020.107615. Retrieved from https://escholarship.umassmed.edu/oapubs/4236
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.