News & Views |
Featured
-
-
News |
Friendly bacteria fight the flu
Microbes trigger immune response that suppresses infections.
- Amy Maxmen
-
News & Views |
Context is key in the gut
The vitamin-A metabolite retinoic acid normally favours immune tolerance in the gut. But in coeliac disease — an intestinal inflammatory disorder due to adverse reactivity to a dietary protein — it may do just the opposite. See Letter p.220
- Craig L. Maynard
- & Casey T. Weaver
-
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
-
Letter |
Functional complementation between FADD and RIP1 in embryos and lymphocytes
Double deficiency of FADD and RIPK1 is shown to rescue the defects in mouse embryonic development and lymphocyte proliferation that are characteristic for mice with single gene deficiencies. This work suggests that the activity of FADD (presumably in conjunction with caspase-8 and c-FLIP) is to keep necrosis in check by causing the cleavage of RIPK1.
- Haibing Zhang
- , Xiaohui Zhou
- & Jianke Zhang
-
Letter |
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers
Using whole-transcriptome sequencing, this paper identifies recurrent gene translocations in B-cell lymphomas that involve the MHC class II transactivator CIITA. These translocations lead to downregulation of cell surface HLA class II expression and, in the case of some fusion partners, overexpression of CD274/CD273 ligands, which have the potential to reduce the antitumour response against these lymphomas.
- Christian Steidl
- , Sohrab P. Shah
- & Randy D. Gascoyne
-
-
Research Highlights |
Modulating malaria's mayhem
-
Letter |
Programming the magnitude and persistence of antibody responses with innate immunity
Here it is shown that nanoparticles containing two Toll-like receptor ligands can boost the magnitude and persistence of vaccine-elicited antibody responses in primates, improving vaccine-mediated protection against influenza virus.
- Sudhir Pai Kasturi
- , Ioanna Skountzou
- & Bali Pulendran
-
Letter |
Coronin 2A mediates actin-dependent de-repression of inflammatory response genes
Activation of inflammatory gene expression by toll-like receptor (TLR) signalling pathways involves the removal of gene repression complexes such as NCoR. Here, coronin 2A, a component of the NCoR complex, is shown to mediate TLR-induced NCoR turnover and de-repression of inflammatory genes by a mechanism involving interaction with oligomeric nuclear actin.
- Wendy Huang
- , Serena Ghisletti
- & Christopher K. Glass
-
Letter |
9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response
A non-coding region on chromosome 9p21 was previously shown to associate with coronary artery disease and type 2 diabetes, and the region has been implicated in regulating neighbouring genes. Here, 33 distinct enhancers within this region are identified, showing that SNPs in one of the enhancers affect STAT1 binding. Furthermore, it is shown that in human vascular endothelial cells the enhancer interval physically interacts with a number of specific loci and that IFN-γ activation strongly affects the chromatin structure and transcriptional regulation of the 9p21 locus, including STAT1 binding, long-range enhancer interactions and expression of neighbouring genes.
- Olivier Harismendy
- , Dimple Notani
- & Kelly A. Frazer
-
Letter |
A thymus candidate in lampreys
Jawless fish were recently shown to possess T- and B-like lymphocytes expressing diverse assembled antigen receptors. This study identifies and characterizes lympho-epithelial thymus-like structures at the tips of gill filaments of lamprey larvae, thus providing evidence that the similarities underlying the adaptive immune systems of both types of vertebrate appear to extend to primary lymphoid organs.
- Baubak Bajoghli
- , Peng Guo
- & Thomas Boehm
-
Research Highlights |
Fooling the heart into repair
-
Books & Arts |
Epidemiology: Epidemic of panic
Autism's broad diagnosis has fuelled fears about vaccines despite no evidence for a link, finds Melvin Konner.
- Melvin Konner
-
Review Article |
Autophagy in immunity and inflammation
- Beth Levine
- , Noboru Mizushima
- & Herbert W. Virgin
-
Research Highlights |
Stronger shields against the flu
-
News & Views |
Peptide gets in shape for self-defence
The transformation of tadpole to frog and of caterpillar to butterfly are two of the more obvious examples of metamorphosis. But molecular shape-shifting may occur in each of us as part of our innate antibacterial defence system. See Letter p.419
- Robert I. Lehrer
-
Letter |
Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1
This paper shows that the activity of human beta-defensin 1 is regulated by its redox status, with enhanced antibiotic killing activity under reducing conditions as they are found in the distal colon. This is believed to serve to protect the healthy intestinal epithelium against potentially harmful colonization by commensal bacteria and opportunistic fungi. In vitro evidence implicates thioredoxin as the likely reducing agent.
- Bjoern O. Schroeder
- , Zhihong Wu
- & Jan Wehkamp
-
Research Highlights |
Neuroimmunology: Immune input for retinal repair
-
Research Highlights |
Cancer: Tumours aided by immune cells
-
Letter |
Oncogenically active MYD88 mutations in human lymphoma
This study finds frequent mutations in MYD88 in the activated B-cell-like subtype of diffuse large B-cell lymphoma and, with lower frequency, in mucosa-associated lymphoid tissue lymphomas. MYD88 mediates signalling by Toll-like receptors, and the mutations, most of which affect the same amino acid, are shown to activate the pathway and promote cancer cell survival.
- Vu N. Ngo
- , Ryan M. Young
- & Louis M. Staudt
-
Letter |
ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks
Although loss of XLF, a classical non-homologous DNA end-joining (NHEJ) repair factor, shows strong effects in non-lymphoid cells, in lymphoid cells its absence has only modest effects on V(D)J recombination. This study now shows that in lymphoid cells, two other repair factors — ATM kinase and histone protein H2AX — have functional redundancy with XLF. Thus, mice deficient in both ATM and XLF have compromised conventional NHEJ, although alternative end-joining is retained. The results hint that the redundant function in end-joining that XLF has with both ATM and H2AX may have to do with an ATM role in chromatin accessibility.
- Shan Zha
- , Chunguang Guo
- & Frederick W. Alt
-
Letter |
H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes
Antigen receptor loci contain numerous gene segments that are recombined in response to antigen stimulation. The RAG endonuclease makes the double-strand breaks that initiate recombination. The ends of these breaks are hairpins that can only be cleaved by the Artemis nuclease. Here, it is shown that the specificity for Artemis is dictated by the histone protein H2AX, in cooperation with the repair protein MDC-1. In the absence of H2AX, another nuclease, CtIP, can open the ends but they are not joined efficiently; this leads to genomic instability.
- Beth A. Helmink
- , Anthony T. Tubbs
- & Barry P. Sleckman
-
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
-
Research Highlights |
Immunology: It's not you. It's your organelles.
-
Letter |
Suppression of inflammation by a synthetic histone mimic
Post-translationally modified histones are recognized by effector proteins which contain specific binding modules; for example, the bromodomain-containing BET proteins bind acetylated lysine residues during gene activation. Here a synthetic small molecule is described that interferes with the binding of certain BET family members to acetylated histones. The compound inhibits activation of pro-inflammatory genes in macrophages and has activity in a mouse model of inflammatory disease.
- Edwige Nicodeme
- , Kate L. Jeffrey
- & Alexander Tarakhovsky
-
Review Article |
The myeloid cells of the central nervous system parenchyma
- Richard M. Ransohoff
- & Astrid E. Cardona
-
News |
Vaccine offers meningitis hope
First affordable and effective weapon against killer meningococcal meningitis A rolled out in Africa.
- Declan Butler
-
Research Highlights |
Immunology: How NETs form to capture invaders
-
News & Views |
Conditional stability of T cells
Data from several recent studies on the dynamics of regulatory T cells — which suppress excessive immune responses — do not add up. Collective analysis of the observations may reconcile the differences between them.
- Shimon Sakaguchi
-
Letter |
The structural basis for membrane binding and pore formation by lymphocyte perforin
Natural killer cells and cytotoxic T cells kill virus-infected and malignant cells, releasing the pore-forming protein perforin in the process. Perforin is required for the delivery of pro-apoptotic granzymes to the target cell. These authors present the crystal structure of a perforin monomer together with a cryo-electron microscopy reconstruction of the oligomeric pore. Perforin monomers within the pore are arranged with an inside-out orientation relative to the structurally homologous monomers of cholesterol-dependent cytolysins.
- Ruby H. P. Law
- , Natalya Lukoyanova
- & James C. Whisstock
-
Letter |
Generation of pathogenic TH17 cells in the absence of TGF-β signalling
CD4+ T cells that selectively produce interleukin (IL)-17 (TH17 cells) are essential for host defence and autoimmunity. It has been thought that IL-6 and transforming growth factor (TGF)-β1 are the factors responsible for initiating the specification of TH17 cells. Here, however, it is shown that TH17 differentiation can occur in the absence of TGF-β signalling. IL-6, IL-23 and IL-1β effectively induced IL-17 production in naive precursors. These data reveal an alternative mode for TH17 differentiation and the importance of IL-23.
- Kamran Ghoreschi
- , Arian Laurence
- & John J. O’Shea
-
Research Highlights |
Immunology: Keeping the peace
-
News & Views |
Egocentric pre–T–cell receptors
The T-cell receptor on the surface of T cells requires antigen recognition to function. Structural studies reveal that its predecessor, the pre-T-cell receptor, is much more independent. See Letter p.844
- Bernard Malissen
- & Hervé Luche
-
Letter |
The structural basis for autonomous dimerization of the pre-T-cell antigen receptor
The pre-T-cell antigen receptor mediates early T-cell development and differentiation. These authors report its structure and explain how the head-to-tail dimeric arrangement allows the interaction of the pre-Tα domain with any variable β domain, and provides the basis for ligand-independent signalling.
- Siew Siew Pang
- , Richard Berry
- & Jamie Rossjohn
-
Letter |
Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis
Apoptotic cells discharge ATP and UTP, which act as 'find-me' signals for phagocytes that in turn engulf dying cells before potentially harmful cellular contents are released. These authors show that the release of ATP and UTP is exclusively by means of the plasma membrane channel pannexin 1, which is opened specifically by caspase activity.
- Faraaz B. Chekeni
- , Michael R. Elliott
- & Kodi S. Ravichandran
-
Research Highlights |
Infectious disease: Battling bacterial blood infection
-
Letter |
Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands
Here it is shown that the end products of lipid oxidation — ω-(2-carboxyethyl) pyrrole and other related pyrroles — are generated during inflammation and wound healing, and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in murine and human melanomas. These carboxyalkylpyrroles are recognized by Toll-like receptor 2 on endothelial cells, setting off a chain of events that leads to the growth of new blood vessels.
- Xiaoxia Z. West
- , Nikolay L. Malinin
- & Tatiana V. Byzova
-
Letter |
Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation
During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. Here, the monoclonal antibodies produced in two infected subjects in response to human immunodeficiency virus (HIV) glycoprotein have been analysed. The results provide evidence for polyreactivity, which may be required when the density of glycoprotein spikes is so low that bivalent binding is unlikely.
- Hugo Mouquet
- , Johannes F. Scheid
- & Michel C. Nussenzweig
-
News & Views |
Antibodies with a split personality
Spikes on the surface of HIV to which antibodies can bind are sparse. One of nature's solutions is to sometimes produce antibodies that bind tightly to a spike with one arm and grab another structure with the other arm. See Letter p.591
- Andreas Plückthun
-
Letter |
Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer
Progestins, used in contraceptives and hormone replacement therapy, have been linked to breast cancer. These authors provide a mechanistic basis for this association. They show in a mouse model that synthetic progestins can promote mammary tumour formation by inducing RANKL (receptor activator of NF-KB ligand), which acts on mammary epithelial cells through the RANKL receptor RANK.
- Daniel Schramek
- , Andreas Leibbrandt
- & Josef M. Penninger
-
News |
Strategy to fight HIV shapes up
A way to nail down the shape of a viral protein segment could spur vaccine development.
- Alla Katsnelson
-
Article |
Gut inflammation provides a respiratory electron acceptor for Salmonella
Salmonella enterica serotype Typhimurium causes acute gut inflammation, which promotes the growth of the pathogen through unknown mechanisms. It is now shown that the reactive oxygen species generated during inflammation react with host-derived sulphur compounds to produce tetrathionate, which the pathogen uses as a terminal electron acceptor to support its growth. The ability to use tetrathionate provides the pathogen with a competitive advantage over bacteria that lack this property.
- Sebastian E. Winter
- , Parameth Thiennimitr
- & Andreas J. Bäumler
-
Research Highlights |
Immunology: Vessels block inflammation
-
Editorial |
The killing fields
Plan to cull badgers in England shows the new government does not respect scientific advice.
-
News & Views |
Inflammation for growth
How does a Salmonella pathogen outcompete beneficial intestinal microorganisms? It triggers an immune response that generates a compound from intestinal gas that it can utilize as an energy source. See Article p. 426
- Samuel I. Miller
-
Letter |
Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance
Immune cells that recognize 'self' tissues need to be eliminated or controlled in order to prevent autoimmune diseases. Here, a T-cell population is delineated that is necessary to maintain self tolerance in mice. Genetic disruption of the inhibitory interaction between these CD8+ T cells and their target Qa-1+ follicular T-helper cells results in a lethal systemic-lupus-erythematosus-like autoimmune disease.
- Hye-Jung Kim
- , Bert Verbinnen
- & Harvey Cantor
-
News |
Statistics spark dismissal suit
Fired researcher's allegations of misconduct prompt university to investigate vaccine trial.
- Emma Marris
-
Letter |
A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells
Human immunodeficiency virus (HIV) fails to induce interferon in the cells that it infects, but the underlying mechanisms are not known. These authors show that the virus can in fact activate the interferon pathway in dendritic cells when the usual block to infection is bypassed. Dendritic cell activation depends on the HIV-1 capsid/cyclophilin A interaction, which is known to have a role in HIV-1 infectivity.
- Nicolas Manel
- , Brandon Hogstad
- & Dan R. Littman
-
Letter |
Oligomeric organization of the B-cell antigen receptor on resting cells
B cells are activated by many different antigens to produce appropriate antibodies. B cells express up to 120,000 B-cell antigen receptor (BCR) complexes on their surface, but how do these complexes remain silent on resting B cells, and how are they activated? It is found here that the BCR on resting cells forms oligomers, and that these may be an autoinhibited form of the receptor. Disruption of the oligomer shifts B cells towards activation.
- Jianying Yang
- & Michael Reth
Browse broader subjects
Browse narrower subjects
- Adaptive immunity
- Antigen processing and presentation
- Antimicrobial responses
- Applied immunology
- Autoimmunity
- Bone marrow transplantation
- Cell death and immune response
- Chemokines
- Coagulation system
- Complement cascade
- Cytokines
- Gene regulation in immune cells
- Haematopoiesis
- Imaging the immune system
- Immune cell death
- Immune evasion
- Immunogenetics
- Immunological disorders
- Immunotherapy
- Infection
- Infectious diseases
- Inflammation
- Innate immune cells
- Innate immunity
- Lymphatic system
- Lymphocytes
- Lymphoid tissues
- Mucosal immunology
- Neuroimmunology
- Osteoimmunology
- Plant immunology
- Signal transduction
- Translational immunology
- Transplant immunology
- Tumour immunology
- Vaccines