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* Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands;
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland;
TopoTarget Switzerland, Lausanne, Switzerland; and
Laboratory of Immunoregulation, University Hospital Ghent, Ghent, Belgium
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-1β 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-1β 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 B.N.L. and J.T. shared supervision over the work.
2 Address correspondence and reprint requests to Dr. Jürg Tschopp, Department of Biochemistry, Chemin des Boveresses 155, 1066 Epalinges, Switzerland. E-mail address: jurg.tschopp{at}unil.ch or Dr. Bart Lambrecht, Laboratory of Immunoregulation, University Hospital Ghent, Ghent, Belgium. E-mail address: bart.lambrecht{at}ugent.be
3 Abbreviations used in this paper: DC, dendritic cell; ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; IPAF, IL-1β-converting enzyme protease activating factor; MLN, mediastinal lymph node; MSU, monosodium urate; NLR, nucleotide-binding oligomerization domain-like receptor; ROS, reactive oxygen species; WT, wild type.
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