Featured
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cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity
Conventional type 1 dendritic cells perform antigen processing and priming of CD4+ and CD8+ T cells against tumour antigens, orchestrating their cross-talk to effect anti-tumour immunity.
- Stephen T. Ferris
- , Vivek Durai
- & Kenneth M. Murphy
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Article |
Extracellular proteostasis prevents aggregation during pathogenic attack
A systematic analysis of the proteostasis network of secreted proteins in Caenorhabditis elegans identifies numerous regulators of protein homeostasis outside the cell, and highlights the contribution of extracellular proteostasis to host defence.
- Ivan Gallotta
- , Aneet Sandhu
- & Della C. David
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Article |
TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7–9
The interaction between TASL and SLC15A4 links endolysosomal Toll-like receptors to the transcription factor IRF5, providing a mechanistic explanation for the involvement of the complex in systemic lupus erythematosus.
- Leonhard X. Heinz
- , JangEun Lee
- & Giulio Superti-Furga
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Article |
Metabolites released from apoptotic cells act as tissue messengers
Apoptotic cells communicate with neighbouring cells by the regulated release of specific metabolites, and a cocktail of select apoptotic metabolites reduces disease severity in mouse models of inflammatory arthritis and lung transplant rejection.
- Christopher B. Medina
- , Parul Mehrotra
- & Kodi S. Ravichandran
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Article |
Activity of caspase-8 determines plasticity between cell death pathways
Alternative cell death pathways are revealed in the absence of caspase-8-dependent apoptosis and MLKL-dependent necroptosis.
- Kim Newton
- , Katherine E. Wickliffe
- & Vishva M. Dixit
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Article |
UNC93B1 recruits syntenin-1 to dampen TLR7 signalling and prevent autoimmunity
The interaction of UNC93B1 with syntenin-1 facilitates the sorting of TLR7–UNC93B1 complexes into intraluminal vesicles of multivesicular bodies, and mutations in UNC93B1 that disrupt such interactions lead to enhanced TLR7 signalling and autoimmunity.
- Olivia Majer
- , Bo Liu
- & Gregory M. Barton
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Article |
Release from UNC93B1 reinforces the compartmentalized activation of select TLRs
The Toll-like receptor TLR9 is activated only after regulated release from its trafficking chaperone UNC93B1, which occurs within endosomes and is required for ligand binding and signal transduction.
- Olivia Majer
- , Bo Liu
- & Gregory M. Barton
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Letter |
DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome
The RNA helicase DDX3X has a critical role in regulating both the induction of stress granules and the activation of the NLRP3 inflammasome in cells under stress conditions.
- Parimal Samir
- , Sannula Kesavardhana
- & Thirumala-Devi Kanneganti
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Letter |
SLC19A1 transports immunoreactive cyclic dinucleotides
A genome-wide CRISPR-interference screen is used to identify the reduced folate carrier SLC19A1 as the major transporter of cyclic dinucleotides in human cells, with potential roles in immunotherapeutic treatment of cancer, immune responses to pathogens and inflammatory diseases.
- Rutger D. Luteijn
- , Shivam A. Zaver
- & David H. Raulet
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Article |
Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity
PIEZO1 signalling mediates activation of a proinflammatory response to cyclical pressure fluctuations in immune cells.
- Angel G. Solis
- , Piotr Bielecki
- & Richard A. Flavell
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Article |
Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome
A cryo-electron microscopy structure of human NLRP3 in complex with the mitotic kinase NEK7 provides insights into the interactions that mediate the activation of the NLRP3 inflammasome.
- Humayun Sharif
- , Li Wang
- & Hao Wu
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Letter |
A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1
A molecular model of STING-mediated signalling is proposed, as structural analysis identifies a crucial motif for the binding of TBK1 to STING, and a separate model involved in IRF-3 binding.
- Baoyu Zhao
- , Fenglei Du
- & Pingwei Li
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Letter |
A NIK–SIX signalling axis controls inflammation by targeted silencing of non-canonical NF-κB
Non-canonical NF-κB is regulated by a negative feedback loop involving NIK-mediated activation of SIX1 and SIX2.
- Zixu Liu
- , Katrina B. Mar
- & Neal M. Alto
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Letter |
Structural basis of STING binding with and phosphorylation by TBK1
The cryo-electron microscopy structure of human TBK1 in complex with cyclic GMP–AMP-bound chicken STING reveals a binding mode that suggests that STING phosphorylation by TBK1 requires oligomerization of both proteins.
- Conggang Zhang
- , Guijun Shang
- & Zhijian J. Chen
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Letter |
Autophagy induction via STING trafficking is a primordial function of the cGAS pathway
The authors report that the cGAS–STING pathway drives a form of autophagy that is independent of interferon induction and distinct from the conventional autophagy.
- Xiang Gui
- , Hui Yang
- & Zhijian J. Chen
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Letter |
Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP–AMP
Cryo-electron microscopy structures of full-length STING show that cyclic GMP–AMP induces a half-turn rotation of the ligand-binding domain relative to the transmembrane domain, forming a tetramer and higher-order oligomers for signalling.
- Guijun Shang
- , Conggang Zhang
- & Xuewu Zhang
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Article |
Bacterial cGAS-like enzymes synthesize diverse nucleotide signals
A bacterial family of cGAS/DncV-like nucleotidyltransferases synthesizes a diverse range of cyclic dinucleotide and trinucleotide compounds that are likely to modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.
- Aaron T. Whiteley
- , James B. Eaglesham
- & Philip J. Kranzusch
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Letter |
Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS–STING signalling
Poxvirus immune nucleases (poxins) degrade 2′,3′-cyclic GMP–AMP that is produced by cyclic GMP–AMP synthase (cGAS) to evade the innate immune system of the host.
- James B. Eaglesham
- , Youdong Pan
- & Philip J. Kranzusch
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Article |
PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation
Recruitment of NLRP3 to the dispersed trans-Golgi network via binding to PtdIns4P is required for activation of the NLRP3 inflammasome by diverse stimuli.
- Jueqi Chen
- & Zhijian J. Chen
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Letter |
Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose
The bacterial metabolite ADP-heptose activates NF-κB in host cells via alpha-kinase 1 and the TIFA–TRAF signalling pathway.
- Ping Zhou
- , Yang She
- & Feng Shao
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Letter |
Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition
Age-dependent epithelial expression of the innate immune receptor TLR5 in the gut of newborn mice selects against the presence of flagellated bacteria and influences microbiota composition throughout life.
- Marcus Fulde
- , Felix Sommer
- & Mathias W. Hornef
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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
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Letter |
Mitochondrial double-stranded RNA triggers antiviral signalling in humans
Mitochondrial double-stranded RNA can induce an interferon response if released into the cytoplasm, but self-recognition is prevented by SUV3 helicase and PNPase exoribonuclease.
- Ashish Dhir
- , Somdutta Dhir
- & Nicholas J. Proudfoot
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Letter |
Targeting STING with covalent small-molecule inhibitors
The discovery and characterization of small-molecule antagonists that inhibit the stimulator of interferon genes (STING) protein may help to develop therapies for the treatment of autoinflammatory disease.
- Simone M. Haag
- , Muhammet F. Gulen
- & Andrea Ablasser
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Letter |
Microglial control of astrocytes in response to microbial metabolites
TGFα and VEGF-B produced by microglia regulate astrocyte function in the experimental autoimmune encephalomyelitis model of multiple sclerosis.
- Veit Rothhammer
- , Davis M. Borucki
- & Francisco J. Quintana
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Article |
Cryo-EM structure of the gasdermin A3 membrane pore
High-resolution cryo-electron microscopy structures of the membrane-pore-forming domain of the mouse gasdermin GSDMA3 show that it forms pores with 26-, 27- or 28-fold symmetry and indicate that it may also form a parallel, soluble, pre-pore ring structure.
- Jianbin Ruan
- , Shiyu Xia
- & Hao Wu
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Letter |
Electrophilic properties of itaconate and derivatives regulate the IκBζ–ATF3 inflammatory axis
The immunoregulatory metabolite itaconate and its dimethyl derivative induce electrophilic stress and react with glutathione to induce both Nrf2-dependent and Nrf2-independent responses, resulting in AF3-mediated inhibition of the inflammation-related protein IκBζ.
- Monika Bambouskova
- , Laurent Gorvel
- & Maxim N. Artyomov
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Letter |
Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus
The C-type lectin receptor MelLec recognizes DHN-melanin in conidial spores of Aspergillus fumigatus and other DHN-melanized fungi, revealing an important role for this receptor in antifungal immunity in both mice and humans.
- Mark H. T. Stappers
- , Alexandra E. Clark
- & Gordon D. Brown
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Letter |
Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation
A report of RNA 5-methylcytosine oxidation by mammalian Tet2, showing that Tet2 promotes infection-induced myelopoiesis in mice via a mechanism involving the repression of Socs3 mRNA, a previously unknown regulatory role of Tet2 at the epitranscriptomic level.
- Qicong Shen
- , Qian Zhang
- & Xuetao Cao
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Letter |
Ubiquitination and degradation of GBPs by a Shigella effector to suppress host defence
A Shigella flexneri type III secretion system effector targets cellular proteins for degradation via the ubiquitin/proteasome pathway, suggesting that such effectors help to overcome defences against bacterial infection.
- Peng Li
- , Wei Jiang
- & Feng Shao
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Letter |
CG dinucleotide suppression enables antiviral defence targeting non-self RNA
Vertebrate genomes contain fewer CG dinucleotides than would be expected by chance, and this pattern is mimicked by many viruses; HIV-1 derivatives mutated to contain more CG dinucleotides are targeted by the human antiviral protein ZAP, suggesting that CG suppression has evolved in viruses to evade recognition.
- Matthew A. Takata
- , Daniel Gonçalves-Carneiro
- & Paul D. Bieniasz
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Letter |
cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein–DNA ladders
A molecular mechanism for the sensitive detection of long and U-turn DNA by cyclic GMP–AMP synthase (cGAS) both in vitro and in human cells.
- Liudmila Andreeva
- , Björn Hiller
- & Karl-Peter Hopfner
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Letter |
cGAS surveillance of micronuclei links genome instability to innate immunity
The cytoplasmic DNA sensor cGAS detects DNA in ruptured micronuclei and activates an innate immune response.
- Karen J. Mackenzie
- , Paula Carroll
- & Andrew P. Jackson
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Letter |
Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells
The inflammasome receptor Nlrp9b defends against enteric viruses by interacting with double-stranded viral RNA-bound helicase Dhx9, triggering gasdermin-D-dependent pyroptotic cell death of infected cells and secretion of Il-18.
- Shu Zhu
- , Siyuan Ding
- & Richard A. Flavell
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Letter |
Global translational reprogramming is a fundamental layer of immune regulation in plants
Global translatome analysis shows that plants also modify their translational output—independently of the changes in transcriptional output—to establish pattern-triggered immunity.
- Guoyong Xu
- , George H. Greene
- & Xinnian Dong
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Letter |
Identification of an atypical monocyte and committed progenitor involved in fibrosis
An atypical monocyte with partial granulocyte characteristics is identified and shown to be critical for the development of fibrosis.
- Takashi Satoh
- , Katsuhiro Nakagawa
- & Shizuo Akira
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Letter |
NLRC3 is an inhibitory sensor of PI3K–mTOR pathways in cancer
Mice deficient in the protein NLRC3 are highly prone to colitis and tumour development in the colon as NLRC3 suppresses the activation of mTOR signalling pathways that help drive tumorigenesis.
- Rajendra Karki
- , Si Ming Man
- & Thirumala-Devi Kanneganti
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Letter |
Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets
Human TRIM5α restricts HIV-1 infection of Langerhans cells through Langerin-dependent autophagy pathway.
- Carla M. S. Ribeiro
- , Ramin Sarrami-Forooshani
- & Teunis B. H. Geijtenbeek
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Letter |
PI3Kγ is a molecular switch that controls immune suppression
Modulation of PI3Kγ activity regulates macrophage polarization during inflammation and cancer, whilst combining PI3Kγ inhibition with immune checkpoint inhibitors leads to synergistic tumour-inhibitory effects.
- Megan M. Kaneda
- , Karen S. Messer
- & Judith A. Varner
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Letter |
Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Caspase-mediated cleavage of gasdermin D, previously shown to mediate pyroptosis, acts by inducing oligomerization and pore formation in cell membranes.
- Xing Liu
- , Zhibin Zhang
- & Judy Lieberman
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Letter |
A core viral protein binds host nucleosomes to sequester immune danger signals
Here, a small core protein of human adenoviruses is shown to associate with histones, sequestering proteins on host chromatin and preventing inflammatory proteins from being released and triggering inflammation.
- Daphne C. Avgousti
- , Christin Herrmann
- & Matthew D. Weitzman
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Letter |
Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion
Antibiotic usage in humans can increase the risk of Salmonella infection by an unknown mechanism; this paper reveals that the antibiotic streptomycin increases the activity of the host-encoded enzyme inducible nitric oxide synthase, this then drives Salmonella expansion by the generation of galactarate — a metabolite normally absent from the gut.
- Franziska Faber
- , Lisa Tran
- & Andreas J. Bäumler
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Brief Communications Arising |
Does caspase-12 suppress inflammasome activation?
- Lieselotte Vande Walle
- , Daniel Jiménez Fernández
- & Mohamed Lamkanfi
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Letter |
Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia
Lypd8 protein derived from intestinal epithelial cells binds to flagellated bacteria to reduce their motility, which limits the entry of Gram-negative bacteria into the inner colonic mucus and prevents invasion of colonic epithelia.
- Ryu Okumura
- , Takashi Kurakawa
- & Kiyoshi Takeda
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Letter |
NOD1 and NOD2 signalling links ER stress with inflammation
A novel link between the unfolded protein response and NOD1/2 innate immune signalling, showing that NOD1/2 are required for ER-stress-induced IL-6 production in response to infection with Brucella abortus.
- A. Marijke Keestra-Gounder
- , Mariana X. Byndloss
- & Renée M. Tsolis
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Letter |
NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux
NEK7, a member of the NIMA-related kinase family, is identified as a regulator of NLRP3 inflammasome oligomerization and activation; NEK7 functions downstream of potassium efflux in a manner that is independent of its kinase activity.
- Yuan He
- , Melody Y. Zeng
- & Gabriel Núñez
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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
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Article |
Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death
CRISPR-Cas9 genome-editing screens identify gasdermin D as a substrate for inflammatory caspases, and its N-terminal cleavage fragment, as well as the equivalent regions in other gasdermins, is shown to be capable of inducing pyroptosis.
- Jianjin Shi
- , Yue Zhao
- & Feng Shao
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Letter |
Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9
Crystal structures of three forms of Toll-like receptor (TLR) 9 — unliganded or bound either to immune stimulatory CpG-containing DNA or inhibitory DNA — together reveal the molecular basis of TLR9 activation.
- Umeharu Ohto
- , Takuma Shibata
- & Toshiyuki Shimizu