Featured
-
-
Article |
Epithelial IFNγ signalling and compartmentalized antigen presentation orchestrate gut immunity
IFNγ signalling in epithelial cells promotes antigen presentation that confers intra-epithelial T cells the ability to limit extracellular ATP and consequent NLRP3 inflammasome activation, controlling pathogenic transformation of CD4+ T cells that promotes colitis and colorectal cancer in mouse models.
- Ankit Malik
- , Deepika Sharma
- & Bana Jabri
-
Article
| Open Access
Structural basis of NINJ1-mediated plasma membrane rupture in cell death
Structural, biochemical and mutagenesis studies indicate that, in dying cells, the membrane protein NINJ1 assembles into filaments, disrupting the cell membrane.
- Morris Degen
- , José Carlos Santos
- & Sebastian Hiller
-
Article |
Cryo-EM structures of the active NLRP3 inflammasome disc
We report cryogenic electron microscopy structures of disc-shaped active NLRP3 oligomers in complex with NEK7 and ASC, and propose that the role of NEK7 is to transform NLRP3 into the active NLRP3 inflammasome disc.
- Le Xiao
- , Venkat Giri Magupalli
- & Hao Wu
-
Article |
Inflammasome activation in infected macrophages drives COVID-19 pathology
A new humanized mouse model for COVID-19 demonstrates SARS-CoV-2 infection and subsequent activation of inflammasomes in human macrophages as a critical driver of disease.
- Esen Sefik
- , Rihao Qu
- & Richard A. Flavell
-
Article |
Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3
Cryo-electron microscopy structures of human NLRP3 in its resting state and bound to the inhibitor CRID3 provide insight into the binding mechanism of CRID3 and its mode of antagonism.
- Inga V. Hochheiser
- , Michael Pilsl
- & Matthias Geyer
-
Article |
DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation
Structures of NLRP1–DPP9 alone and with a small-molecule inhibitor of DPP9 reveal the mechanisms through which NLRP1 is regulated, providing insights into the role of this complex in inflammasome regulation.
- L. Robert Hollingsworth
- , Humayun Sharif
- & Hao Wu
-
Article |
The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis
Accelerated atherosclerosis in a mouse model of clonal haematopoiesis is prevented by genetic interruption of AIM2 inflammasome activation or by inhibition of interleukin-1β.
- Trevor P. Fidler
- , Chenyi Xue
- & Alan R. Tall
-
Article |
NINJ1 mediates plasma membrane rupture during lytic cell death
The small transmembrane protein NINJ1 promotes plasma membrane rupture in lytic cell death associated with pyroptosis, necrosis and apoptosis.
- Nobuhiko Kayagaki
- , Opher S. Kornfeld
- & Vishva M. Dixit
-
Article |
Galactosaminogalactan activates the inflammasome to provide host protection
Galactosaminogalactan of Aspergillus fumigatus acts as a pathogen-associated molecular pattern that activates the NLRP3 inflammasome, which is crucial for anti-fungal host defence.
- Benoit Briard
- , Thierry Fontaine
- & Thirumala-Devi Kanneganti
-
Article |
Gasdermin E suppresses tumour growth by activating anti-tumour immunity
The gasdermin E protein is shown to act as a tumour suppressor: it is cleaved by caspase 3 and granzyme B and leads to pyroptosis of cancer cells, provoking an immune response to the tumour.
- Zhibin Zhang
- , Ying Zhang
- & Judy Lieberman
-
Article |
New mitochondrial DNA synthesis enables NLRP3 inflammasome activation
New mitochondrial DNA synthesis links the priming and activation of the NLRP3 inflammasome.
- Zhenyu Zhong
- , Shuang Liang
- & Michael Karin
-
Letter |
Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing
Lipolysis declines with age because NLRP3 inflammasome-activated adipose tissue macrophages reduce levels of noradrenaline by upregulating genes that control its degradation, such as GDF3 and MAOA.
- Christina D. Camell
- , Jil Sander
- & Vishwa Deep Dixit
-
Brief Communications Arising |
Does caspase-12 suppress inflammasome activation?
- Lieselotte Vande Walle
- , Daniel Jiménez Fernández
- & Mohamed Lamkanfi
-
Article |
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Gasdermin D is identified as the required substrate for pyroptosis, mediating caspase-11 function in the non-canonical inflammasome pathway; the cleaved N-terminal domain is shown to trigger pyroptosis.
- Nobuhiko Kayagaki
- , Irma B. Stowe
- & Vishva M. Dixit
-
Letter |
Dietary modulation of the microbiome affects autoinflammatory disease
Pstpip2-mutant mice fed a high-fat diet are protected against inflammatory bone disease and bone erosion; this protection is associated with reductions in intestinal Prevotella levels and pro-IL-1β expression, and is dependent on the deletion of both caspases 1 and 8.
- John R. Lukens
- , Prajwal Gurung
- & Thirumala-Devi Kanneganti
-
Article |
Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection
Quiescent CD4 T cells in lymphoid tissues are shown to die after HIV-1 infection by caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death; caspase 1 inhibitors, which are safe for human use, can rescue the cell death in vitro raising the possibility of new therapeutics targeting the host instead of the virus.
- Gilad Doitsh
- , Nicole L. K. Galloway
- & Warner C. Greene
-
Outlook |
Inflammation: A complex problem
Multi-protein inflammasomes are being implicated in a surprising number of diseases, and researchers are keen to find out why.
- Katharine Gammon
-
Letter |
NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Alzheimer’s-prone mice deficient in NLRP3 or caspase-1 fail to develop learning deficits and show reduced neuropathology.
- Michael T. Heneka
- , Markus P. Kummer
- & Douglas T. Golenbock
-
Letter |
The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP
Evidence is presented that activation of the NLRP3 inflammasome is regulated by the calcium-sensing receptor (CASR).
- Geun-Shik Lee
- , Naeha Subramanian
- & Jae Jin Chae
-
Letter |
IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine
IL-22 is one of the factors that, although important for wound healing, also promote tumorigenesis; the regulation of IL-22BP, the IL-22 binding protein, via the NLRP3 and NLRP6 inflammasomes provides an unanticipated mechanism, controlling IL-22 and thereby the development of colon cancer.
- Samuel Huber
- , Nicola Gagliani
- & Richard A. Flavell
-
Letter |
Rapid induction of inflammatory lipid mediators by the inflammasome in vivo
Induction of an eicosanoid storm is shown to be an unexpected consequence of inflammasome activation in peritoneal macrophages, leading to vascular leakage and rapid death in mice.
- Jakob von Moltke
- , Norver J. Trinidad
- & Russell E. Vance
-
Letter |
Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1
Activation of the non-canonical, pro-inflammatory caspase-11 by Salmonella typhimurium is shown to contribute to bacterial spread and pathogenesis by the induction of macrophage cell death.
- Petr Broz
- , Thomas Ruby
- & Denise M. Monack
-
Letter |
Novel role of PKR in inflammasome activation and HMGB1 release
Double-stranded RNA-dependent protein kinase (PKR) is shown to be a key regulator of the inflammasome; PKR is central for caspase-1 activation and the release of interleukin (IL)-1β, IL-18 and high-mobility group box 1 (HMGB1) in response to a diverse range of stimuli.
- Ben Lu
- , Takahisa Nakamura
- & Kevin J. Tracey
-
Article |
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
An expansion of Porphyromonadaceae in the gut is linked to the pathogenesis and progression of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in the mouse.
- Jorge Henao-Mejia
- , Eran Elinav
- & Richard A. Flavell
-
Review Article |
Inflammasomes in health and disease
- Till Strowig
- , Jorge Henao-Mejia
- & Richard Flavell
-
Letter |
Non-canonical inflammasome activation targets caspase-11
- Nobuhiko Kayagaki
- , Søren Warming
- & Vishva M. Dixit
-
News & Views |
Recognition of a unique partner
The mammalian immune system can fight a myriad of pathogens. In part, this involves a superfamily of cytoplasmic receptors that dictate assembly of specific pro-inflammatory inflammasome complexes. See Letters p.592 & p.596
- Denise M. Monack
-
Letter |
The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus
- Yue Zhao
- , Jieling Yang
- & Feng Shao
-
Letter |
Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity
- Eric M. Kofoed
- & Russell E. Vance
-
News & Views |
In command of commensals
Humans must maintain a balanced composition for the trillions of commensal microbes that inhabit their gut, but how they do this is largely unclear. It now emerges that one factor is a molecular pathway in gut epithelial cells.
- Menno van Lookeren Campagne
- & Vishva M. Dixit
-
News |
Friendly bacteria fight the flu
Microbes trigger immune response that suppresses infections.
- Amy Maxmen
-
Letter |
A role for mitochondria in NLRP3 inflammasome activation
Mitochondrial reactive oxygen species are shown to be required for activation of the NLRP3 inflammasome by various stimuli.
- Rongbin Zhou
- , Amir S. Yazdi
- & Jürg Tschopp
-
Letter |
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
During atherosclerosis, crystals of cholesterol accumulate in atherosclerotic plaques. But are they a consequence or a cause of the inflammation associated with the disease? Here it is shown that small cholesterol crystals appear early in the development of atherosclerosis, and that they act as an endogenous danger signal, causing inflammation by activating the NLRP3 inflammasome pathway. Cholesterol crystals thus seem to be an early cause, rather than a late consequence, of inflammation.
- Peter Duewell
- , Hajime Kono
- & Eicke Latz
Recognition and maturation of IL-18 by caspase-4 noncanonical inflammasome