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PMID: 18768827 Published · ppublish English Journal Article

Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 181 ·No. 6 ·2008-09-15 ·Pages 3755-9

Kool M, Pétrilli V, De Smedt T, Rolaz A, Hammad H, van Nimwegen M, Bergen IM, Castillo R, Lambrecht BN, Tschopp J

Abstract

Adjuvants are vaccine additives that stimulate the immune system without having any specific antigenic effect of itself. In this study we show that alum adjuvant induces the release of IL-1beta from macrophages and dendritic cells and that this is abrogated in cells lacking various NALP3 inflammasome components. The NALP3 inflammasome is also required in vivo for the innate immune response to OVA in alum. The early production of IL-1beta and the influx of inflammatory cells into the peritoneal cavity is strongly reduced in NALP3-deficient mice. The activation of adaptive cellular immunity to OVA-alum is initiated by monocytic dendritic cell precursors that induce the expansion of Ag-specific T cells in a NALP3-dependent way. We propose that, in addition to TLR stimulators, agonists of the NALP3 inflammasome should also be considered as vaccine adjuvants.

MeSH Terms
Adjuvants, Immunologic/pharmacology Alum Compounds/pharmacology Aluminum Hydroxide/pharmacology Animals Carrier Proteins/biosynthesis,genetics,physiology Dendritic Cells/immunology,metabolism,pathology Female Immunologic Factors/pharmacology Inflammation Mediators/pharmacology Macrophage Activation/immunology Macrophages, Peritoneal/immunology,metabolism,pathology Magnesium Hydroxide/pharmacology Male Mice Mice, Inbred C57BL Mice, Knockout NLR Family, Pyrin Domain-Containing 3 Protein
Chemicals
Adjuvants, Immunologic Alum Compounds Carrier Proteins Immunologic Factors Inflammation Mediators NLR Family, Pyrin Domain-Containing 3 Protein Nlrp3 protein, mouse Aluminum Hydroxide Magnesium Hydroxide
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Kool Mirjam
Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Pétrilli Virginie
De Smedt Thibaut
Rolaz Aline
Hammad Hamida
van Nimwegen Menno
Bergen Ingrid M
Castillo Rosa
Lambrecht Bart N
Tschopp Jürg
Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
Published
2008-09-15
Pages
3755-9
Language
English
Region
United States
NLM ID
2985117R
Subset
IM
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