Featured
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Letter |
Rapid fucosylation of intestinal epithelium sustains host–commensal symbiosis in sickness
Systemic exposure to Toll-like receptor (TLR) ligands during sickness is shown to induce fucosylation of the small intestine in mice; some of the fucose is shed into the intestinal lumen, where it provides nourishment for the microbiota.
- Joseph M. Pickard
- , Corinne F. Maurice
- & Alexander V. Chervonsky
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Article |
AhR sensing of bacterial pigments regulates antibacterial defence
The mammalian aryl hydrocarbon receptor (known to sense environmental pollutants) is shown to also have a role as a pattern recognition receptor in sensing bacterial virulence factors, resulting in an antibacterial response and activation of innate and natural defences.
- Pedro Moura-Alves
- , Kellen Faé
- & Stefan H. E. Kaufmann
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Letter |
Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5′-diphosphates
The innate immune receptor RIG-I is shown to sense 5′-diphosphate RNAs as found in some viral genomes in addition to its well characterized activation by RNAs bearing 5′-triphosphate moieties.
- Delphine Goubau
- , Martin Schlee
- & Caetano Reis e Sousa
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Article |
Inflammatory caspases are innate immune receptors for intracellular LPS
Caspase-4 and caspase-11 are shown to be the direct sensors for cytoplasmic lipopolysaccharide in humans and mice, respectively, mediating inflammatory cell death in intracellular bacterial infection.
- Jianjin Shi
- , Yue Zhao
- & Feng Shao
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Article |
Aryl hydrocarbon receptor control of a disease tolerance defence pathway
Initial exposure to lipopolysaccharide (LPS) induces endotoxin tolerance, which reduces immunological reactions to LPS; here it is shown that primary LPS challenge is controlled by AhR, TDO2 and IL-10, whereas sustained effects require AhR, IDO1 and TGF-β, allowing for disease tolerance with reduced immunopathology in infections.
- Alban Bessede
- , Marco Gargaro
- & Paolo Puccetti
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Letter |
Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression
The timing of type I interferon signalling determines the disease course of SIV infection.
- Netanya G. Sandler
- , Steven E. Bosinger
- & Daniel C. Douek
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Letter |
Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis
Pathogenesis of rheumatoid arthritis depends critically on the NLRP3 inflammasome/interleukin-1 signalling axis.
- Lieselotte Vande Walle
- , Nina Van Opdenbosch
- & Mohamed Lamkanfi
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Letter |
Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome
The Pyrin inflammasome detects the presence of a pathogen not through recognition of a microbial molecule but by the activity of a bacterial toxin that modifies host Rho activity.
- Hao Xu
- , Jieling Yang
- & Feng Shao
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Letter |
Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases
Interferon-inducible GTPases are required for the release of vacuolar Gram-negative bacteria into the cytoplasm and subsequent inflammasome-mediated caspase-11 activation.
- Etienne Meunier
- , Mathias S. Dick
- & Petr Broz
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Letter |
Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I
RIG-I protein recognizes viral duplex RNA with a 5′-triphosphate group, activating innate immune responses; a crystal structure of its tetrameric CARD signalling domain reveals that non-covalently linked ubiquitin chains stabilize the tetramer in a ‘lock-washer’ structure that serves as a signalling platform for the recruitment and activation of MAVS.
- Alys Peisley
- , Bin Wu
- & Sun Hur
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Letter |
Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity
Tissue-resident macrophages are shown to stop lipopolysaccharide-induced inflammation by spreading an anti-inflammatory calcium signal to alveolar epithelial cells through connexin-43-positive gap junction channels.
- Kristin Westphalen
- , Galina A. Gusarova
- & Jahar Bhattacharya
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Letter |
Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP
The cytoplasmic DNA receptor cGAS catalyses the synthesis of the second messenger cGAMP, which in turn activates type I interferon via STING; this study shows that cGAMP is transmitted to neighbouring cells via gap junction channels and activates STING, thus inducing an antiviral state in these bystander cells independent of paracrine interferon signalling.
- Andrea Ablasser
- , Jonathan L. Schmid-Burgk
- & Veit Hornung
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Letter |
DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance
In Caenorhabditis elegans, genome instability in the form of exogenous and endogenous DNA damage in germ cells evokes elevated heat- and oxidative-stress resistance in somatic tissues; this is mediated by MPK-1, which triggers the induction of putative secreted peptides associated with innate immunity, leading to activation of the ubiquitin–proteasome system.
- Maria A. Ermolaeva
- , Alexandra Segref
- & Björn Schumacher
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Letter |
cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING
Cytosolic DNA induces type I interferon via activation of STING; the immediate STING activator is produced by the recently identified DNA sensor cGAS and is shown here to be an unorthodox cyclic dinucleotide harbouring a 2′-5′ linkage between guanosine and adenosine.
- Andrea Ablasser
- , Marion Goldeck
- & Veit Hornung
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Article |
Structural mechanism of cytosolic DNA sensing by cGAS
Cytosolic DNA arising from intracellular bacterial or viral infections induces type I interferon through activation of the DNA sensor cGAS, which catalyses the synthesis of cyclic dinucleotide which in turn activates STING; here the crystal structures of a carboxy-terminal fragment of cGAS alone and in complex with UTP and DNA–ATP–GTP complex are determined.
- Filiz Civril
- , Tobias Deimling
- & Karl-Peter Hopfner
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Letter |
A CRISPR/Cas system mediates bacterial innate immune evasion and virulence
The CRISPR/Cas system known to aid bacterial defences by targeting invading DNA can also act to evade eukaryotic defences through a different class of small RNAs downregulating an endogenous immunogenic bacterial lipoprotein.
- Timothy R. Sampson
- , Sunil D. Saroj
- & David S. Weiss
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Letter |
Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1
Salmonella effector proteins trigger host innate immunity through the activation of small Rho GTPases, which, in turn, is sensed by the NOD1/2 signalling pathway.
- A. Marijke Keestra
- , Maria G. Winter
- & Andreas J. Bäumler
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Letter |
A T-bet gradient controls the fate and function of CCR6−RORγt+ innate lymphoid cells
The graded expression of the transcription factor T-bet in CCR6−RORγt+ innate lymphoid cells is found to be involved in the control of interferon-γ expression, a cytokine that is required to protect the epithelial barrier against Salmonella infections.
- Christoph S. N. Klose
- , Elina A. Kiss
- & Andreas Diefenbach
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Article |
Structural basis for viral 5′-PPP-RNA recognition by human IFIT proteins
Crystal structures reveal insight into how interferon-induced proteins with tetratricopeptide repeats (IFITs) selectively recognize viral RNA.
- Yazan M. Abbas
- , Andreas Pichlmair
- & Bhushan Nagar
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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
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Letter |
Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin
Chronic inflammation is a feature of the ageing brain and some neurodegenerative diseases; the authors show that astrocytes normally suppress neuroinflammation through activation of their DRD2 receptor by CRYAB, potentially opening new avenues for treatments.
- Wei Shao
- , Shu-zhen Zhang
- & Jia-wei Zhou
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Letter |
Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells
Neurons and oligodendrocytes differentiated from induced pluripotent stem cells (iPSCs) of patients with inherited TLR3 and UNC-93B deficiencies are found to be more susceptible to infection by HSV-1 than control cells because they fail to induce a normal interferon response, whereas neural stem cells and astrocytes are not susceptible.
- Fabien G. Lafaille
- , Itai M. Pessach
- & Luigi D. Notarangelo
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Brief Communications Arising |
Yeretssian et al. reply
- Garabet Yeretssian
- , Ricardo G. Correa
- & Maya Saleh
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Brief Communications Arising |
Is BID required for NOD signalling?
- Ueli Nachbur
- , James E. Vince
- & John Silke
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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
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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
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Letter |
Phosphorylation of NLRC4 is critical for inflammasome activation
Phosphorylation of the NOD-like receptor NLRC4 is essential for activation of the NLRC4 inflammasome complex in response to bacterial stimuli.
- Yan Qu
- , Shahram Misaghi
- & Vishva M. Dixit
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Letter |
NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens
The Nod-like receptor family member NLRP6 is characterized and shown to be a negative regulator of inflammatory signalling, dampening host responses against bacterial infections and impeding bacterial clearance.
- Paras K. Anand
- , R. K. Subbarao Malireddi
- & Thirumala-Devi Kanneganti
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Perspective |
Allergic host defences
A review of allergic host defences argues that allergic immunity has an important role in host defence against noxious environmental substances.
- Noah W. Palm
- , Rachel K. Rosenstein
- & Ruslan Medzhitov
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Research Highlights |
Fighting viruses antibody-free
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Correspondence |
Nobels: Toll pioneers deserve recognition
- James P. Allison
- , Christophe Benoist
- & Alexander V. Chervonsky
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Letter |
Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B
- Julian P. Vivian
- , Renee C. Duncan
- & Jamie Rossjohn
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Letter |
Non-canonical inflammasome activation targets caspase-11
- Nobuhiko Kayagaki
- , Søren Warming
- & Vishva M. Dixit
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Article |
Complement factor H binds malondialdehyde epitopes and protects from oxidative stress
- David Weismann
- , Karsten Hartvigsen
- & Christoph J. Binder
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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
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Letter |
STING is a direct innate immune sensor of cyclic di-GMP
- Dara L. Burdette
- , Kathryn M. Monroe
- & Russell E. Vance
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Letter |
Structural basis of RNA recognition and activation by innate immune receptor RIG-I
- Fuguo Jiang
- , Anand Ramanathan
- & Joseph Marcotrigiano
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Letter |
The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus
- Yue Zhao
- , Jieling Yang
- & Feng Shao
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Letter |
Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity
- Eric M. Kofoed
- & Russell E. Vance
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Research Highlights |
Virus detected upon entry
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Letter |
Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein
- Kasia Hrecka
- , Caili Hao
- & Jacek Skowronski
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Research Highlights |
Cells sense house dust
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Letter |
Detection of prokaryotic mRNA signifies microbial viability and promotes immunity
- Leif E. Sander
- , Michael J. Davis
- & J. Magarian Blander
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Letter |
Non-apoptotic role of BID in inflammation and innate immunity
- Garabet Yeretssian
- , Ricardo G. Correa
- & Maya Saleh
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Letter |
Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’
- Helen S. Goodridge
- , Christopher N. Reyes
- & David M. Underhill
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Letter |
TLR signalling augments macrophage bactericidal activity through mitochondrial ROS
- A. Phillip West
- , Igor E. Brodsky
- & Sankar Ghosh
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Letter |
TRIM5 is an innate immune sensor for the retrovirus capsid lattice
- Thomas Pertel
- , Stéphane Hausmann
- & Jeremy Luban
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News & Views |
Innate immunity cues virulence
Salmonella intestinal pathogens employ a clever trick. They use the immune response that their host triggers to destroy them to enhance the expression of genes that mediate the pathogens' virulence.
- Michelle M. C. Buckner
- & B. Brett Finlay
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News & Views |
Culprit within a culprit
The parasitic infection mucocutaneous leishmaniasis can vary in severity. It emerges that the levels of an RNA virus within the parasite affect both the host's immune response and the parasite's persistence.
- Martin Olivier