Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants.

Abstract:

:Aluminium adjuvants, typically referred to as 'alum', are the most commonly used adjuvants in human and animal vaccines worldwide, yet the mechanism underlying the stimulation of the immune system by alum remains unknown. Toll-like receptors are critical in sensing infections and are therefore common targets of various adjuvants used in immunological studies. Although alum is known to induce the production of proinflammatory cytokines in vitro, it has been repeatedly demonstrated that alum does not require intact Toll-like receptor signalling to activate the immune system. Here we show that aluminium adjuvants activate an intracellular innate immune response system called the Nalp3 (also known as cryopyrin, CIAS1 or NLRP3) inflammasome. Production of the pro-inflammatory cytokines interleukin-1beta and interleukin-18 by macrophages in response to alum in vitro required intact inflammasome signalling. Furthermore, in vivo, mice deficient in Nalp3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) or caspase-1 failed to mount a significant antibody response to an antigen administered with aluminium adjuvants, whereas the response to complete Freund's adjuvant remained intact. We identify the Nalp3 inflammasome as a crucial element in the adjuvant effect of aluminium adjuvants; in addition, we show that the innate inflammasome pathway can direct a humoral adaptive immune response. This is likely to affect how we design effective, but safe, adjuvants in the future.

journal_name

Nature

journal_title

Nature

authors

Eisenbarth SC,Colegio OR,O'Connor W,Sutterwala FS,Flavell RA

doi

10.1038/nature06939

subject

Has Abstract

pub_date

2008-06-19 00:00:00

pages

1122-6

issue

7198

eissn

0028-0836

issn

1476-4687

pii

nature06939

journal_volume

453

pub_type

杂志文章

相关文献

NATURE文献大全
  • Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.

    abstract::Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-l...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature05945

    authors: Soda M,Choi YL,Enomoto M,Takada S,Yamashita Y,Ishikawa S,Fujiwara S,Watanabe H,Kurashina K,Hatanaka H,Bando M,Ohno S,Ishikawa Y,Aburatani H,Niki T,Sohara Y,Sugiyama Y,Mano H

    更新日期:2007-08-02 00:00:00

  • Requirement for nerve growth factor in the development of myelinated nociceptors in vivo.

    abstract::In adult animals, sensory neurons innervating the skin are phenotypically diverse. We have now investigated whether nerve growth factor (NGF) has a physiological role in the development of this diversity. We gave antisera against NGF to rats from postnatal day 1 (PND 1) to adulthood (5 weeks). We found a virtually com...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/350500a0

    authors: Ritter AM,Lewin GR,Kremer NE,Mendell LM

    更新日期:1991-04-11 00:00:00

  • Production of dimethylfuran for liquid fuels from biomass-derived carbohydrates.

    abstract::Diminishing fossil fuel reserves and growing concerns about global warming indicate that sustainable sources of energy are needed in the near future. For fuels to be useful in the transportation sector, they must have specific physical properties that allow for efficient distribution, storage and combustion; these pro...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature05923

    authors: Román-Leshkov Y,Barrett CJ,Liu ZY,Dumesic JA

    更新日期:2007-06-21 00:00:00

  • Glia-derived neurons are required for sex-specific learning in C. elegans.

    abstract::Sex differences in behaviour extend to cognitive-like processes such as learning, but the underlying dimorphisms in neural circuit development and organization that generate these behavioural differences are largely unknown. Here we define at the single-cell level-from development, through neural circuit connectivity,...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature15700

    authors: Sammut M,Cook SJ,Nguyen KCQ,Felton T,Hall DH,Emmons SW,Poole RJ,Barrios A

    更新日期:2015-10-15 00:00:00

  • Origins and functional evolution of Y chromosomes across mammals.

    abstract::Y chromosomes underlie sex determination in mammals, but their repeat-rich nature has hampered sequencing and associated evolutionary studies. Here we trace Y evolution across 15 representative mammals on the basis of high-throughput genome and transcriptome sequencing. We uncover three independent sex chromosome orig...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature13151

    authors: Cortez D,Marin R,Toledo-Flores D,Froidevaux L,Liechti A,Waters PD,Grützner F,Kaessmann H

    更新日期:2014-04-24 00:00:00

  • The product of the Drosophila gene vasa is very similar to eukaryotic initiation factor-4A.

    abstract::The vasa gene product of Drosophila melanogaster is required only in the female germ line. Progeny of females homozygous for vasa mutations lack posterior structures and pole cells. Isolation and characterization of vasa genomic and complementary DNA clones show that the transcript is abundant in the female germ line ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/335611a0

    authors: Lasko PF,Ashburner M

    更新日期:1988-10-13 00:00:00

  • Magnetoelectrics: is CdCr2S4 a multiferroic relaxor?

    abstract::Materials showing simultaneous ferroelectric and magnetic ordering are attracting a great deal of interest because of their unusual physics and potential applications. Hemberger et al. have reported relaxor-like dielectric properties and colossal magnetocapacitance (in excess of 500%) for the cubic spinel compound CdC...

    journal_title:Nature

    pub_type: 评论,杂志文章

    doi:10.1038/nature06156

    authors: Catalan G,Scott JF

    更新日期:2007-08-23 00:00:00

  • MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters.

    abstract::The T-cell immune response is directed against antigenic peptide fragments generated in intracellular compartments, the cytosol or the endocytic system. Peptides derived from cytosolic proteins, usually of biosynthetic origin, are presented efficiently to T-cell receptors by major histocompatibility complex (MHC) clas...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/348738a0

    authors: Deverson EV,Gow IR,Coadwell WJ,Monaco JJ,Butcher GW,Howard JC

    更新日期:1990-12-20 00:00:00

  • Co-evolution and plant resistance to natural enemies.

    abstract::Co-evolution between plants and their natural enemies is generally believed to have generated much of the Earth's biological diversity. A process analogous to co-evolution occurs in agricultural systems, in which natural enemies adapt to crop resistance introduced by breeding or genetic engineering. Because of this si...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35081193

    authors: Rausher MD

    更新日期:2001-06-14 00:00:00

  • Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells.

    abstract::Haemophilia B, or Christmas disease, is an inherited X-chromosome-linked bleeding disorder caused by a defect in clotting factor IX and occurs in about 1 in 30,000 males in the United Kingdom. Injection of factor IX concentrate obtained from blood donors allows most patients to be successfully managed. However, becaus...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/315683a0

    authors: Anson DS,Austen DE,Brownlee GG

    更新日期:1985-06-20 00:00:00

  • Neuronal synchrony does not correlate with motion coherence in cortical area MT.

    abstract::Natural visual scenes are cluttered with multiple objects whose individual features must somehow be selectively linked (or 'bound') if perception is to coincide with reality. Recent neurophysiological evidence supports a 'binding-by-synchrony' hypothesis: neurons excited by features of the same object fire synchronous...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature01285

    authors: Thiele A,Stoner G

    更新日期:2003-01-23 00:00:00

  • A primitive therizinosauroid dinosaur from the Early Cretaceous of Utah.

    abstract::Therizinosauroids are an enigmatic group of dinosaurs known mostly from the Cretaceous period of Asia, whose derived members are characterized by elongate necks, laterally expanded pelves, small, leaf-shaped teeth, edentulous rostra and mandibular symphyses that probably bore keratinized beaks. Although more than a do...

    journal_title:Nature

    pub_type: 历史文章,杂志文章

    doi:10.1038/nature03468

    authors: Kirkland JI,Zanno LE,Sampson SD,Clark JM,DeBlieux DD

    更新日期:2005-05-05 00:00:00

  • Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies.

    abstract::One reason for the failure of chemotherapy in the treatment of advanced cancers may be the outgrowth of multidrug-resistant tumour cells. Multidrug resistance has been modelled in numerous mammalian cell lines in which the phenotype is characterized by a pleiotropic cross-resistance to unrelated drugs. In the study re...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/316820a0

    authors: Kartner N,Evernden-Porelle D,Bradley G,Ling V

    更新日期:1985-08-29 00:00:00

  • Modes of faulting at mid-ocean ridges.

    abstract::Abyssal-hill-bounding faults that pervade the oceanic crust are the most common tectonic feature on the surface of the Earth. The recognition that these faults form at plate spreading centres came with the plate tectonic revolution. Recent observations reveal a large range of fault sizes and orientations; numerical mo...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature03358

    authors: Buck WR,Lavier LL,Poliakov AN

    更新日期:2005-04-07 00:00:00

  • Constraints on the composition of the Earth's core from ab initio calculations

    abstract::Knowledge of the composition of the Earth's core is important for understanding its melting point and therefore the temperature at the inner-core boundary and the temperature profile of the core and mantle. In addition, the partitioning of light elements between solid and liquid, as the outer core freezes at the inner...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35012056

    authors: Alfe D,Gillan MJ,Price GD

    更新日期:2000-05-11 00:00:00

  • Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11.

    abstract::In mammals, one of the most pronounced consequences of viral infection is the induction of type I interferons, cytokines with potent antiviral activity. Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes (ISGs) that are also induced directly by pathogens via the interferon regulatory fact...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11433

    authors: Li M,Kao E,Gao X,Sandig H,Limmer K,Pavon-Eternod M,Jones TE,Landry S,Pan T,Weitzman MD,David M

    更新日期:2012-11-01 00:00:00

  • How thick is the lithosphere?

    abstract::A rapid decrease in shear velocity in the suboceanic mantle is used to infer the thickness of the lithosphere. It is proposed that new and highly precise group velocity data constrain the solutions and imply a thickness near 70 km. ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/226330a0

    authors: Kanamori H,Press F

    更新日期:1970-04-25 00:00:00

  • Osteoprotection by semaphorin 3A.

    abstract::The bony skeleton is maintained by local factors that regulate bone-forming osteoblasts and bone-resorbing osteoclasts, in addition to hormonal activity. Osteoprotegerin protects bone by inhibiting osteoclastic bone resorption, but no factor has yet been identified as a local determinant of bone mass that regulates bo...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11000

    authors: Hayashi M,Nakashima T,Taniguchi M,Kodama T,Kumanogoh A,Takayanagi H

    更新日期:2012-05-03 00:00:00

  • Cortical substrates for exploratory decisions in humans.

    abstract::Decision making in an uncertain environment poses a conflict between the opposing demands of gathering and exploiting information. In a classic illustration of this 'exploration-exploitation' dilemma, a gambler choosing between multiple slot machines balances the desire to select what seems, on the basis of accumulate...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature04766

    authors: Daw ND,O'Doherty JP,Dayan P,Seymour B,Dolan RJ

    更新日期:2006-06-15 00:00:00

  • A language-specific comprehension strategy.

    abstract::Infants acquire whatever language is spoken in the environment into which they are born. The mental capability of the newborn child is not biased in any way towards the acquisition of one human language rather than another. Because psychologists who attempt to model the process of language comprehension are interested...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/304159a0

    authors: Cutler A,Mehler J,Norris D,Segui J

    更新日期:1983-07-14 00:00:00

  • Functional V region formation during in vitro culture of a murine immature B precursor cell line.

    abstract::B lymphocytes originate from pluripotential haematopoietic stem cells and differentiate into immunoglobulin (Ig)-producing cells. B-cell lineage differentiation is accompanied by two types of immunoglobulin gene rearrangements--rearrangement of V, D and J gene segments to create a functional V gene and rearrangement o...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/303812a0

    authors: Sugiyama H,Akira S,Kikutani H,Kishimoto S,Yamamura Y,Kishimoto T

    更新日期:1983-06-30 00:00:00

  • Krox-20 controls myelination in the peripheral nervous system.

    abstract::The molecular mechanisms controlling the process of myelination by Schwann cells remain elusive, despite recent progress in the identification and characterization of genes encoding myelin components (reviewed in ref. 1). We have created a null allele in the mouse Krox-20 gene, which encodes a zinc-finger transcriptio...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/371796a0

    authors: Topilko P,Schneider-Maunoury S,Levi G,Baron-Van Evercooren A,Chennoufi AB,Seitanidou T,Babinet C,Charnay P

    更新日期:1994-10-27 00:00:00

  • Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission.

    abstract::Genetic manipulations of insect populations for pest control have been advocated for some time, but there are few cases where manipulated individuals have been released in the field and no cases where they have successfully invaded target populations. Population transformation using the intracellular bacterium Wolbach...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature10356

    authors: Hoffmann AA,Montgomery BL,Popovici J,Iturbe-Ormaetxe I,Johnson PH,Muzzi F,Greenfield M,Durkan M,Leong YS,Dong Y,Cook H,Axford J,Callahan AG,Kenny N,Omodei C,McGraw EA,Ryan PA,Ritchie SA,Turelli M,O'Neill SL

    更新日期:2011-08-24 00:00:00

  • eIF5B gates the transition from translation initiation to elongation.

    abstract::Translation initiation determines both the quantity and identity of the protein that is encoded in an mRNA by establishing the reading frame for protein synthesis. In eukaryotic cells, numerous translation initiation factors prepare ribosomes for polypeptide synthesis; however, the underlying dynamics of this process ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-019-1561-0

    authors: Wang J,Johnson AG,Lapointe CP,Choi J,Prabhakar A,Chen DH,Petrov AN,Puglisi JD

    更新日期:2019-09-01 00:00:00

  • Developmental plasticity and the origin of tetrapods.

    abstract::The origin of tetrapods from their fish antecedents, approximately 400 million years ago, was coupled with the origin of terrestrial locomotion and the evolution of supporting limbs. Polypterus is a member of the basal-most group of ray-finned fish (actinopterygians) and has many plesiomorphic morphologies that are co...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature13708

    authors: Standen EM,Du TY,Larsson HC

    更新日期:2014-09-04 00:00:00

  • Designing metallic glass matrix composites with high toughness and tensile ductility.

    abstract::The selection and design of modern high-performance structural engineering materials is driven by optimizing combinations of mechanical properties such as strength, ductility, toughness, elasticity and requirements for predictable and graceful (non-catastrophic) failure in service. Highly processable bulk metallic gla...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature06598

    authors: Hofmann DC,Suh JY,Wiest A,Duan G,Lind ML,Demetriou MD,Johnson WL

    更新日期:2008-02-28 00:00:00

  • Anomalous structure in the single particle spectrum of the fractional quantum Hall effect.

    abstract::The two-dimensional electron system is a powerful laboratory for investigating the physics of interacting particles. Application of a large magnetic field produces massively degenerate quantum levels known as Landau levels; within a Landau level the kinetic energy of the electrons is suppressed, and electron-electron ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature08941

    authors: Dial OE,Ashoori RC,Pfeiffer LN,West KW

    更新日期:2010-03-25 00:00:00

  • Hinf family: a novel repeated DNA family of the human genome.

    abstract::The isolation of a mutant adenovirus carrying an insertion of cellular DNA has led to the identification of a new family of human repetitive sequences, which are found tandemly arranged in the genome. The sequence of the viral insert resembles that of eukaryotic transposable elements. ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/302587a0

    authors: Shimizu Y,Yoshida K,Ren CS,Fujinaga K,Rajagopalan S,Chinnadurai G

    更新日期:1983-04-14 00:00:00

  • Communications: quantum teleportation across the Danube.

    abstract::Efficient long-distance quantum teleportation is crucial for quantum communication and quantum networking schemes. Here we describe the high-fidelity teleportation of photons over a distance of 600 metres across the River Danube in Vienna, with the optimal efficiency that can be achieved using linear optics. Our resul...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/430849a

    authors: Ursin R,Jennewein T,Aspelmeyer M,Kaltenbaek R,Lindenthal M,Walther P,Zeilinger A

    更新日期:2004-08-19 00:00:00

  • Fluvial response to abrupt global warming at the Palaeocene/Eocene boundary.

    abstract::Climate strongly affects the production of sediment from mountain catchments as well as its transport and deposition within adjacent sedimentary basins. However, identifying climatic influences on basin stratigraphy is complicated by nonlinearities, feedback loops, lag times, buffering and convergence among processes ...

    journal_title:Nature

    pub_type: 历史文章,杂志文章

    doi:10.1038/nature11513

    authors: Foreman BZ,Heller PL,Clementz MT

    更新日期:2012-11-01 00:00:00