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Schweneker, K.* ; Gorka, O.* ; Schweneker, M.* ; Poeck, H.* ; Tschopp, J.* ; Peschel, C.* ; Ruland, J. ; Groß, O.*

The mycobacterial cord factor adjuvant analogue trehalose-6,6'-dibehenate (TDB) activates the Nlrp3 inflammasome.

Immunobiology 218, 664-673 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The success of a vaccine consists in the induction of an innate immune response and subsequent activation of the adaptive immune system. Because antigens are usually not immunogenic, the addition of adjuvants that activate innate immunity is required. The mycobacterial cord factor trehalose-6,6'-dimycolate (TDM) and its synthetic adjuvant analogue trehalose-6,6'-dibehenate (TDB) rely on the C-type lectin Mincle and the signaling molecules Syk and Card9 to trigger innate immunity. In this study, we show that stimulation of bone marrow-derived dendritic cells (BMDCs) with TDB induces Nlrp3 inflammasome-dependent IL-1β secretion. While Card9 is required for NF-κB activation by TDB, it is dispensable for TDB-induced activation of the Nlrp3 inflammasome. Additionally, efflux of intracellular potassium, lysosomal rupture, and oxygen radical (ROS) production are crucial for caspase-1 processing and IL-1β secretion by TDB. In an in vivo inflammation model, we demonstrate that the recruitment of neutrophils by TDB is significantly reduced in the Nlrp3-deficient mice compared to the wild-type mice, while the production of chemokines in vitro is not influenced by the absence of Nlrp3. These results identify the Nlrp3 inflammasome as an essential mediator for the induction of an innate immune response triggered by TDB.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Inflammasome; Nlrp3; Tubercolosis; Adjuvant; TDB; Nf-kappa-b ; Innate Immune-response ; Nalp3 Inflammasome ; Vaccine Adjuvants ; Cutting Edge ; Tuberculosis ; Stimulation ; Caspase-1 ; Adapters ; Pathways
ISSN (print) / ISBN 0171-2985
e-ISSN 1878-3279
Journal Immunobiology : Experimental and Clinical
Quellenangaben Volume: 218, Issue: 4, Pages: 664-673 Article Number: , Supplement: ,
Publisher Urban & Fischer
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)