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Platelets Fuel the Inflammasome Activation of Innate Immune Cells

Rolfes, V;Ribeiro, LS;Hawwari, I;Bttcher, L;Rosero, N;Maasewerd, S;Santos, MLS;Prchnicki, T;Silva, CMS;Wanderley, CWS;Rothe, M;Schmidt, SV;Stunden, HJ;Bertheloot, D;Rivas, MN;Fontes, CJ;Carvalho, LH;Cunha, FQ;Latz, E;Arditi, M;Franklin, BS;

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 invitro, neglecting the influence of cellular interactions that occur invivo. 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-1 secretion. Platelets influence IL-1 production invivo, and blood platelet counts correlate with plasmatic IL-1 levels in malaria. Furthermore, we reveal an enriched platelet gene signature among the highest-expressed transcripts in IL-1-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. Copyright 2020 The Author(s). Published by Elsevier Inc. All rights reserved.