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Platelets Fuel the Inflammasome Activation of Innate Immune Cells

72 Pages Posted: 21 Aug 2019 Sneak Peek Status: Under Review

See all articles by Verena Rolfes

Verena Rolfes

University of Bonn - Institute of Innate Immunity

Lucas S. Ribeiro

University of Bonn - Institute of Innate Immunity

Ibrahim Hawwari

University of Bonn - Institute of Innate Immunity

Lisa Böttcher

University of Bonn - Institute of Innate Immunity

Nathalia Rosero

University of Bonn - Institute of Innate Immunity

Salie Maasewerd

University of Bonn - Institute of Innate Immunity

Marina Lima S. Santos

Instituto René Rachou - Laboratório de Malária

Susanne V. Schmidt

University of Bonn - Institute of Innate Immunity

Maximilian Rothe

University of Bonn - Institute of Innate Immunity

H. James Stunden

University of Bonn - Institute of Innate Immunity

Luzia H. Carvalho

Fundação Oswaldo Cruz - Laboratório de Malária

Cor J. Fontes

Universidade Federal de Mato Grosso - Departamento de Clínica Médica

Moshe Arditi

Cedars Sinai Medical Center - Departments of Pediatrics and Biomedical Sciences

Eicke Latz

German Center for Neurodegenerative Diseases (DZNE); University of Bonn - Institute of Innate Immunity; University of Massachusetts Worcester - Department of Medicine

Bernardo S. Franklin

University of Bonn - Institute of Innate Immunity

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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 homogenous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets, the second most abundant cells in the blood, 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 nucleation, caspase-1 activity, and IL-1β maturation. Platelet depletion attenuated LPS-induced IL-1β in vivo, and platelet counts correlate with plasma concentrations of IL-1β in malaria patients. Furthermore, a platelet gene signature was enriched among the highest expressed transcripts in IL-1β-driven autoinflammatory diseases. The platelet-mediated enhancement of inflammasome activation was independent of cell-to-cell contacts, platelet-derived lipid mediators, purines, nucleic acids and a host of platelet cytokines, and involved the triggering of calcium sensing receptors on macrophages by a calcium-dependent protein commonly released by platelets and megakaryocytes. Finally, we report that platelets provide an additional layer of regulation of inflammasomes in vivo.

Keywords: Inflammasomes, interleukin-1, auto-inflammatory diseases, platelets, malaria, NLRP3

Suggested Citation

Rolfes, Verena and Ribeiro, Lucas S. and Hawwari, Ibrahim and Böttcher, Lisa and Rosero, Nathalia and Maasewerd, Salie and Santos, Marina Lima S. and Schmidt, Susanne V. and Rothe, Maximilian and Stunden, H. James and Carvalho, Luzia H. and Fontes, Cor J. and Arditi, Moshe and Latz, Eicke and Franklin, Bernardo S., Platelets Fuel the Inflammasome Activation of Innate Immune Cells (August 20, 2019). CELL-REPORTS-D-19-03149. Available at SSRN: https://ssrn.com/abstract=3439682 or http://dx.doi.org/10.2139/ssrn.3439682
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Verena Rolfes

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Lucas S. Ribeiro

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Ibrahim Hawwari

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Lisa Böttcher

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Nathalia Rosero

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Salie Maasewerd

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Marina Lima S. Santos

Instituto René Rachou - Laboratório de Malária

Brazil

Susanne V. Schmidt

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Maximilian Rothe

University of Bonn - Institute of Innate Immunity

Bonn
Germany

H. James Stunden

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Luzia H. Carvalho

Fundação Oswaldo Cruz - Laboratório de Malária

Brazil

Cor J. Fontes

Universidade Federal de Mato Grosso - Departamento de Clínica Médica

Mato Grosso
Brazil

Moshe Arditi

Cedars Sinai Medical Center - Departments of Pediatrics and Biomedical Sciences

Los Angeles, CA
United States

Eicke Latz

German Center for Neurodegenerative Diseases (DZNE)

von Siebold Strasse 3a
Goettingen, 37075
Germany

University of Bonn - Institute of Innate Immunity

Bonn
Germany

University of Massachusetts Worcester - Department of Medicine

55 Lake Avenue North
Worcester, MA 01655
United States

Bernardo S. Franklin (Contact Author)

University of Bonn - Institute of Innate Immunity

Bonn
Germany

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