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2035-01-01
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PLATELETS FUEL THE INFLAMMASOME ACTIVATION OF INNATE IMMUNE CELLS
interleukin-1
platelets
auto-inflammatory diseases
malaria
NLRP3
ASC
Caspase-1
Cell Death
Pyroptosis
Author
Rolfes, Verena
Ribeiro, Lucas Secchim
Hawwari, Ibrahim
Böttcher, Lisa
Rosero, Nathalia
Maasewerd, Salie
Santos, Marina Lima Silva
Próchnicki, Tomasz
Silva, Camila Meirelles de Souza
Wanderley, Carlos Wagner de Souza
Rothe, Maximilian
Schmidt, Susanne V.
Stunden, H. James
Bertheloot, Damien
Rivas, Magali Noval
Fontes, Cor Jesus
Carvalho, Luzia Helena
Cunha, Fernando Queiroz
Latz, Eicke
Arditi, Moshe
Franklin, Bernardo Simoes
Ribeiro, Lucas Secchim
Hawwari, Ibrahim
Böttcher, Lisa
Rosero, Nathalia
Maasewerd, Salie
Santos, Marina Lima Silva
Próchnicki, Tomasz
Silva, Camila Meirelles de Souza
Wanderley, Carlos Wagner de Souza
Rothe, Maximilian
Schmidt, Susanne V.
Stunden, H. James
Bertheloot, Damien
Rivas, Magali Noval
Fontes, Cor Jesus
Carvalho, Luzia Helena
Cunha, Fernando Queiroz
Latz, Eicke
Arditi, Moshe
Franklin, Bernardo Simoes
Affilliation
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brazil
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Centro de Pesquisa em Doenças Inflamatórias. Ribeirão Preto, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Centro de Pesquisa em Doenças Inflamatórias. Ribeirão Preto, SP, Brasil
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Departments of Pediatrics, Division of Infectious Diseases and Immunology, and Infectious and Immunologic Diseases Research Center (IIDRC. Department of Biomedical Sciences. Cedars-Sinai Medical Center, Los Angeles, CA
Universidade Federal de Mato Grosso. Departamento de Clínica Médica. Cuiabá, MT, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brazil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Centro de Pesquisa em Doenças Inflamatórias. Ribeirão Preto, SP, Brazil
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany/Department of Infectious Diseases and Immunology. University of Massachusetts Medical School. Worcester, MA 01655, USA/German Center for Neurodegenerative Diseases. 53127 Bonn, NRW, Germany
Departments of Pediatrics, Division of Infectious Diseases and Immunology, and Infectious and Immunologic Diseases Research Center (IIDRC. Department of Biomedical Sciences. Cedars-Sinai Medical Center, Los Angeles, CA
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brazil
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Centro de Pesquisa em Doenças Inflamatórias. Ribeirão Preto, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Centro de Pesquisa em Doenças Inflamatórias. Ribeirão Preto, SP, Brasil
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
Departments of Pediatrics, Division of Infectious Diseases and Immunology, and Infectious and Immunologic Diseases Research Center (IIDRC. Department of Biomedical Sciences. Cedars-Sinai Medical Center, Los Angeles, CA
Universidade Federal de Mato Grosso. Departamento de Clínica Médica. Cuiabá, MT, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brazil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Centro de Pesquisa em Doenças Inflamatórias. Ribeirão Preto, SP, Brazil
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany/Department of Infectious Diseases and Immunology. University of Massachusetts Medical School. Worcester, MA 01655, USA/German Center for Neurodegenerative Diseases. 53127 Bonn, NRW, Germany
Departments of Pediatrics, Division of Infectious Diseases and Immunology, and Infectious and Immunologic Diseases Research Center (IIDRC. Department of Biomedical Sciences. Cedars-Sinai Medical Center, Los Angeles, CA
Institute of Innate Immunity. Medical Faculty. University of Bonn. 53127 Bonn, NRW, Germany
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-1β secretion. Platelets influence IL-1β production in vivo, and blood platelet counts correlate with plasmatic IL-1β levels in malaria. Furthermore, we reveal an enriched platelet gene signature among the highest-expressed transcripts in IL-1β-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
inflammasomesinterleukin-1
platelets
auto-inflammatory diseases
malaria
NLRP3
ASC
Caspase-1
Cell Death
Pyroptosis
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