Priming Is Dispensable for NLRP3 Inflammasome Activation in Human Monocytes


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2020
Historique:
received: 26 05 2020
accepted: 14 09 2020
entrez: 26 10 2020
pubmed: 27 10 2020
medline: 4 6 2021
Statut: epublish

Résumé

Interleukin (IL)-18 and IL-1β are potent pro-inflammatory cytokines that contribute to inflammatory conditions such as rheumatoid arthritis and Alzheimer's disease. They are produced as inactive precursors that are activated by large macromolecular complexes called inflammasomes upon sensing damage or pathogenic signals. NLRP3 inflammasome activation is regarded to require a priming step that causes NLRP3 and IL-1β gene upregulation, and also NLRP3 post-translational licencing. A subsequent activation step leads to the assembly of the complex and the cleavage of pro-IL-18 and pro-IL-1β by caspase-1 into their mature forms, allowing their release. Here we show that human monocytes, but not monocyte derived macrophages, are able to form canonical NLRP3 inflammasomes in the absence of priming. NLRP3 activator nigericin caused the processing and release of constitutively expressed IL-18 in an unprimed setting. This was mediated by the canonical NLRP3 inflammasome that was dependent on K

Identifiants

pubmed: 33101286
doi: 10.3389/fimmu.2020.565924
pmc: PMC7555430
doi:

Substances chimiques

GSDMD protein, human 0
Inflammasomes 0
Interleukin-18 0
Interleukin-1beta 0
Intracellular Signaling Peptides and Proteins 0
NLR Family, Pyrin Domain-Containing 3 Protein 0
Phosphate-Binding Proteins 0
Caspase 1 EC 3.4.22.36
Nigericin RRU6GY95IS

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

565924

Subventions

Organisme : Medical Research Council
ID : MR/N029992/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N013751/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 110091
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104192/Z/14/Z
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2020 Gritsenko, Yu, Martin-Sanchez, Diaz-del-Olmo, Nichols, Davis, Brough and Lopez-Castejon.

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Auteurs

Anna Gritsenko (A)

Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Shi Yu (S)

Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Fatima Martin-Sanchez (F)

Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Ines Diaz-Del-Olmo (I)

Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Eva-Maria Nichols (EM)

Adaptive Immunity Research Unit, GSK, Stevenage, United Kingdom.

Daniel M Davis (DM)

Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

David Brough (D)

Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Gloria Lopez-Castejon (G)

Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

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Classifications MeSH