ILC2s - resident lymphocytes pre-adapted to a specific tissue or migratory effectors that adapt to where they move?
Abstract A cardinal feature of the T-cell adaptive immune system is the antigen-dependent activation of naïve T cells in secondary lymphoid sites, followed by the migration of the resultant effector cells through the efferent lymph to the blood and then into a peripheral tissue site of infection or tumor growth. In contrast, the current view of innate lymphocytes (ILCs), the innate counterparts of T cells, is that they are tissue-resident cells, adapted to their specific environments during development and performing their effector functions locally upon cytokine stimulation. Here we present recent findings t...
Source: Current Opinion in Immunology - November 22, 2018 Category: Allergy & Immunology Authors: Germain RN, Huang Y Tags: Curr Opin Immunol Source Type: research

Updates on autoinflammatory diseases.
Abstract Autoinflammatory diseases are hyperinflammatory, immune dysregulatory diseases caused by innate immune cells dysregulation that present typically in the perinatal period with systemic and organ-targeted inflammation, but with improved genetic testing and the development of diagnostic criteria, milder and later-onset forms are being detected in adulthood. While the discovery of gain-of-function mutations in innate sensors linked to the production of proinflammatory cytokines provided the bases for anti-cytokine therapies that changed disease and patient outcomes, the field is expanding with the increasing ...
Source: Current Opinion in Immunology - November 16, 2018 Category: Allergy & Immunology Authors: Martinez-Quiles N, Goldbach-Mansky R Tags: Curr Opin Immunol Source Type: research

Bridging the gap between vaccination with Bacille Calmette-Gu érin (BCG) and immunological tolerance: the cases of type 1 diabetes and multiple sclerosis.
Bridging the gap between vaccination with Bacille Calmette-Guérin (BCG) and immunological tolerance: the cases of type 1 diabetes and multiple sclerosis. Curr Opin Immunol. 2018 Nov 14;55:89-96 Authors: Ristori G, Faustman D, Matarese G, Romano S, Salvetti M Abstract At the end of past century, when the prevailing view was that treatment of autoimmunity required immune suppression, experimental evidence suggested an approach of immune-stimulation such as with the BCG vaccine in type 1 diabetes (T1D) and multiple sclerosis (MS). Translating these basic studies into clinical trials, we showed the...
Source: Current Opinion in Immunology - November 14, 2018 Category: Allergy & Immunology Authors: Ristori G, Faustman D, Matarese G, Romano S, Salvetti M Tags: Curr Opin Immunol Source Type: research

Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control.
Abstract Lambda interferons (IFNλs, type III IFNs or interleukins-28/29) were described fifteen years ago as novel cytokines sharing structural and functional homology with IL-10 and type I IFNs, respectively. IFNλs engage a unique receptor complex comprising IFNLR1 and IL10R2, nevertheless they share signaling cascade and many functions with type I IFNs, questioning their possible non-redundant roles and overall biological importance. Here, we review the latest evidence establishing the primacy of IFNλs in front line protection at anatomical barriers, mediating antiviral immunity before type ...
Source: Current Opinion in Immunology - November 3, 2018 Category: Allergy & Immunology Authors: Andreakos E, Zanoni I, Galani IE Tags: Curr Opin Immunol Source Type: research

The long and the short of it: insights into the cellular source of autoantibodies as revealed by B cell depletion therapy.
Abstract High titers of pathogenic autoantibodies are a hallmark of many autoimmune diseases. However, much remains unknown about the self-reactive plasma cells that are key mediators of disease. We propose a model in which the varying efficacy of precursor B cell depletion for the treatment of humoral autoimmunity can be explained by differences in the relative contributions of pathogenic antibodies by short-lived versus long-lived plasma cells. Beyond therapeutic considerations, this model suggests that we can infer the cellular source of disease-associated autoantibodies by the durability of serum titers follow...
Source: Current Opinion in Immunology - October 31, 2018 Category: Allergy & Immunology Authors: Hale M, Rawlings DJ, Jackson SW Tags: Curr Opin Immunol Source Type: research

Age (autoimmunity) associated B cells (ABCs) and their relatives.
Abstract B cells affect human and animal health in numerous ways. They are the precursors for the antibody-secreting plasma cells and they also take up antigen, particularly antigen for which they bear-specific receptors, very efficiently and thus present antigen to T cells. The T cell-B cell interactions that thus occur serve not only to affect the B cell, but also, the T cell partner of the interaction. B cells are known to be quite heterogeneous. The different subpopulations of B cells contribute to different types of immune responses. Over the last 20 years it has become apparent that some B cells unexpectedly...
Source: Current Opinion in Immunology - October 30, 2018 Category: Allergy & Immunology Authors: Phalke S, Marrack P Tags: Curr Opin Immunol Source Type: research

Dead or alive: how the immune system detects microbial viability.
Abstract Immune detection of microbial viability is increasingly recognized as a potent driver of innate and adaptive immune responses. Here we describe recent mechanistic insights into the process of how the immune system discriminates between viable and non-viable microbial matter. Accumulating evidence suggests a key role for microbial RNA as a widely conserved viability associated PAMP (vita-PAMP) and a molecular signal of increased infectious threat. Toll-like receptor 8 (TLR8) has recently emerged as a critical sensor for viable bacteria, ssRNA viruses, and archaea in human antigen presenting cells (APC). We...
Source: Current Opinion in Immunology - October 23, 2018 Category: Allergy & Immunology Authors: Ugolini M, Sander LE Tags: Curr Opin Immunol Source Type: research

Antiviral resistance of stem cells.
Abstract Stem cells are important for growth and regeneration given their ability to self-renew and differentiate into mature cells. Resistance to certain viral infections has been established as a phenotype of stem cells, a protection in line with their important physiological function. Antiviral resistance is critical to all cells, but it is differentially regulated between stem cells and differentiated cells. Stem cells utilize antiviral RNA interference, interferon-independent repression of endogenous retroviruses and intrinsic expression of antiviral interferon-stimulated genes. Differentiated cells often rel...
Source: Current Opinion in Immunology - October 20, 2018 Category: Allergy & Immunology Authors: Wu X, Kwong AC, Rice CM Tags: Curr Opin Immunol Source Type: research

Epigenetic dynamics in normal and malignant B cells: die a hero or live to become a villain.
Abstract Normal B cell development, activation, and terminal differentiation depend on the intricate dynamics of cooperating epigenetic and non-coding components to control the level and timing of expression of thousands of genes. Recent genome-wide studies have integratively mapped changes in the chromatin landscape, DNA methylome, 3-dimensional interactome, and coding and non-coding transcriptomes of normal and malignant B cells. Genetic ablation in human cells and mouse models has begun to elucidate the coordinated roles of essential epigenetic modifiers, key transcription factors, and long non-coding RNAs in B...
Source: Current Opinion in Immunology - October 17, 2018 Category: Allergy & Immunology Authors: Andrews JM, Payton JE Tags: Curr Opin Immunol Source Type: research

Oxeiptosis: a discreet way to respond to radicals.
Abstract One of the best-studied cellular responses to toxic signals and pathogens is programmed cell death. Over the past years, it became apparent that the specific mechanisms of cell death have tremendous influence at both cellular and organismal level, highlighting the importance of sensors and pathways involved in this decision-making process. Central signalling molecules involved in a variety of cell death pathways are reactive oxygen species (ROS). However, the molecular mechanisms regulating differential responses and cellular fates to distinct ROS levels remain incompletely understood. Recently, we uncove...
Source: Current Opinion in Immunology - October 17, 2018 Category: Allergy & Immunology Authors: Scaturro P, Pichlmair A Tags: Curr Opin Immunol Source Type: research

Innate immune priming of insulin secretion.
Abstract Increasing evidence suggests a role for the immune system to finely tune metabolic homeostasis. The possibility that the immune system can likewise regulate islet endocrine function has only commenced drawing attention. Islet beta cells are the main producers of insulin and have to dynamically respond to fluctuating insulin demands of the body. While inflammation has long been considered as an important pathogenic feature of diabetes development, pioneer studies have shown that immune cells reside inside pancreatic islets under steady state and that components of the immune system can promote beta cell in...
Source: Current Opinion in Immunology - October 17, 2018 Category: Allergy & Immunology Authors: Dalmas E Tags: Curr Opin Immunol Source Type: research

Regulation of metabolic supply and demand during B cell activation and subsequent differentiation.
Abstract B cell activation and differentiation are associated with marked changes in proliferative and effector functions. Each stage of B cell differentiation thus has unique metabolic demands. New studies have provided insight on how nutrient uptake and usage by B cells are regulated by B cell receptor signals, autophagy, mammalian target of rapamycin, and transcriptional control of transporters and rate-limiting enzymes. A recurring theme is that these pathways play distinct roles ranging from survival to antibody production, depending on the B cell fate. We review recently published data that define how these ...
Source: Current Opinion in Immunology - October 16, 2018 Category: Allergy & Immunology Authors: Egawa T, Bhattacharya D Tags: Curr Opin Immunol Source Type: research

From zero to sixty and back to zero again: the metabolic life of B cells.
Abstract Throughout their lifetimes B cells shift metabolic gears to move rapidly from quiescent states to full out proliferative expansion and back again. Here we discuss recent findings that shed light on how B cells rapidly shift gears to metabolically fuel expansion and then just as rapidly down shift during phases of receptor rearrangements to ensure genome stability. We also discuss the link between metabolic activity and fate decisions in B cells. PMID: 30312894 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 9, 2018 Category: Allergy & Immunology Authors: Akkaya M, Pierce SK Tags: Curr Opin Immunol Source Type: research

Innate immunosensing of DNA in cellular senescence.
r A Abstract Senescence is a multistep cellular program featuring a stable cell cycle arrest, which occurs upon exposure to various stressors. Senescent cells exhibit metabolic activity and hypertrophy and produce a multitude of factors with both cell intrinsic as well as non-cell autonomous functions. These factors are collectively referred to as the senescence-associated secretory phenotype (SASP). Recently, the DNA sensor cyclic GMP AMP synthase (cGAS) and the adaptor stimulator of interferon genes (STING) have been reported to be critically involved in the regulation of senescence. This suggests that cGAS has ...
Source: Current Opinion in Immunology - October 5, 2018 Category: Allergy & Immunology Authors: Glück S, Ablasser A Tags: Curr Opin Immunol Source Type: research

SAMHD1 and the innate immune response to cytosolic DNA during DNA replication.
Abstract Cytosolic DNA of endogenous or exogenous origin is sensed by the cGAS-STING pathway to activate innate immune responses. Besides microbial DNA, this pathway detects self-DNA in the cytoplasm of damaged or abnormal cells and plays a central role in antitumor immunity. The mechanism by which cytosolic DNA accumulates under genotoxic stress conditions is currently unclear, but recent studies on factors mutated in the Aicardi-Goutières syndrome cells, such as SAMHD1, RNase H2 and TREX1, are shedding new light on this key process. In particular, these studies indicate that the rupture of micronuclei and...
Source: Current Opinion in Immunology - October 4, 2018 Category: Allergy & Immunology Authors: Coquel F, Neumayer C, Lin YL, Pasero P Tags: Curr Opin Immunol Source Type: research

Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance.
Abstract A substantial fraction of mature naïve B cells recognize endogenous antigens, and this autoreactivity must be controlled to prevent autoantibody secretion. Selective downregulation of the IgM BCR on autoreactive B cells has long been appreciated, and recent findings illustrate how this might impose tolerance. The BCR isotype maintained on autoreactive B cells, IgD, is less sensitive to endogenous antigens than IgM. This reduced sensitivity may be conferred by structural properties of IgD and/or differential association with activating and inhibitory co-receptors. Once activated, autoreactive B cells ...
Source: Current Opinion in Immunology - October 4, 2018 Category: Allergy & Immunology Authors: Noviski M, Zikherman J Tags: Curr Opin Immunol Source Type: research

Natural regulatory plasma cells.
Abstract B cells can generate several types of antibody-secreting cells, including plasmablasts that divide and are short lived, as well as plasma cells that do not proliferate and can persist for extended time periods. Here, we discuss the identification of a novel subset of non-dividing plasma cells specialized in the production of interleukin(IL)-10. These cells develop at steady state, including in germ-free mice, via a mechanism dependent on the B cell receptor for antigen and possibly involving the recognition of damaged cells. They are characterized by the expression of the inhibitory receptor LAG-3, and al...
Source: Current Opinion in Immunology - October 3, 2018 Category: Allergy & Immunology Authors: Fillatreau S Tags: Curr Opin Immunol Source Type: research

LAP it up, fuzz ball: a short history of LC3-associated phagocytosis.
Abstract LC3-associated phagocytosis (LAP) exists at the crossroads of the two evolutionary pathways of phagocytosis and autophagy. When a phagocyte engulfs an extracellular particle that engages receptor signaling, components of the autophagy machinery and Rubicon are recruited to the cargo-containing phagosome or LAPosome. Formation of the LAPosome is critical for both cargo clearance as well as mediating the proper signaling cascade. Globally, LAP functions as an immunosuppressive mechanism, as LAP deficiency often results in hyperinflammation. As defects in the autophagy machinery have been long associated wit...
Source: Current Opinion in Immunology - October 1, 2018 Category: Allergy & Immunology Authors: Martinez J Tags: Curr Opin Immunol Source Type: research

Reprogramming of mitochondrial metabolism by innate immunity.
Abstract The reprogramming of cellular metabolism has emerged as a major aspect of innate immune cell activation. Mitochondria, which are well known for their critical functions in cellular bioenergetics and metabolism, also serve innate immune purposes by providing specific signaling platforms. Latest advances in our understanding of innate immune receptor-mediated metabolic reprogramming have unraveled specific immune functions of mitochondrial metabolites that place mitochondrial metabolism and particularly the mitochondrial respiratory chain at the center of innate immunity. This review highlights some recent ...
Source: Current Opinion in Immunology - October 1, 2018 Category: Allergy & Immunology Authors: Garaude J Tags: Curr Opin Immunol Source Type: research

Regulation of lymphocyte trafficking in central nervous system autoimmunity.
Abstract CD4+ T helper (Th) cells play a central role in orchestrating protective immunity but also in autoimmunity. Multiple Sclerosis (MS) is a human autoimmune disease of the central nervous system (CNS) characterized by the infiltration of inflammatory lymphocytes and myeloid cells into the brain and spinal cord, leading to demyelination, axonal damage, and progressive loss of motor functions. The release of T cells in the circulation and their migration in the central nervous system are key and tightly regulated processes which have been targeted to decrease CD4+ T cell presence in the CNS and limit disease p...
Source: Current Opinion in Immunology - September 27, 2018 Category: Allergy & Immunology Authors: Oukka M, Bettelli E Tags: Curr Opin Immunol Source Type: research

Coagulopathies and inflammatory diseases:'…glimpse of a Snark'.
Coagulopathies and inflammatory diseases: '…glimpse of a Snark'. Curr Opin Immunol. 2018 Sep 27;55:44-53 Authors: Del Carmen S, Hapak SM, Ghosh S, Rothlin CV Abstract Coagulopathies and inflammatory diseases, ostensibly, have distinct underlying molecular bases. Notwithstanding, both are host defense mechanisms to physical injury. In invertebrates, clotting can function directly in anti-pathogen defense. Molecules of the vertebrate clotting cascade have also been directly linked to the regulation of inflammation. We posit that thrombophilia may provide resistance against pathogens in vertebrate...
Source: Current Opinion in Immunology - September 27, 2018 Category: Allergy & Immunology Authors: Del Carmen S, Hapak SM, Ghosh S, Rothlin CV Tags: Curr Opin Immunol Source Type: research

DNA as a self-antigen: nature and regulation.
Abstract High-affinity antibodies to double-stranded DNA are a hallmark of systemic lupus erythematosus (SLE) and are thought to contribute to disease flares and tissue inflammation such as nephritis. Notwithstanding their clinical importance, major questions remain about the development and regulation of these pathogenic anti-DNA responses. These include the mechanisms that prevent anti-DNA responses in healthy subjects, despite the constant generation of self-DNA and the abundance of DNA-reactive B cells; the nature and physical form of antigenic DNA in SLE; the regulation of DNA availability as an antigen; and ...
Source: Current Opinion in Immunology - September 24, 2018 Category: Allergy & Immunology Authors: Soni C, Reizis B Tags: Curr Opin Immunol Source Type: research

Microbiota - an amplifier of autoimmunity.
Abstract Many studies describe dysbiosis as a change in the microbiota that accompanies autoimmune illnesses, but little is known about whether these changes are a cause or consequence of an altered immune state. The immune system actively shapes the composition of the microbiota, with divergent outcomes in healthy or autoimmune-prone individuals. The gut microbiota in turn acts as an acquired endocrine organ, influencing the physiology of the host via release of nutrients and chemical messengers. Dysbiosis arising from abnormal immune function can initiate or amplify autoimmunity through multiple mechanisms. We e...
Source: Current Opinion in Immunology - September 21, 2018 Category: Allergy & Immunology Authors: Vogelzang A, Guerrini MM, Minato N, Fagarasan S Tags: Curr Opin Immunol Source Type: research

Extracellular matrix and the maintenance and loss of peripheral immune tolerance in autoimmune insulitis.
Abstract There is a growing appreciation that the extracellular matrix (ECM) contributes to both the maintenance of immune tolerance in healthy tissues and to its loss at sites of autoimmunity. Here, we review recent literature on the role of ECM and particularly the glycosaminoglycans hyaluronan and heparan sulfate in the development of autoimmune, type 1 diabetes (T1D). Data from transplant models suggest that healthy islets are embedded within an intact ECM that supports beta-cell homeostasis and provides physical and immunoregulatory barriers against immune infiltration. However, studies of human insulitis as ...
Source: Current Opinion in Immunology - September 21, 2018 Category: Allergy & Immunology Authors: Medina CO, Nagy N, Bollyky PL Tags: Curr Opin Immunol Source Type: research

IL-6: a cytokine at the crossroads of autoimmunity.
Abstract IL-6 is implicated in the development and progression of autoimmune diseases in part by influencing CD4 T cell lineage and regulation. Elevated IL-6 levels drive inflammation in a wide range of autoimmune diseases, some of which are also characterized by enhanced T cell responses to IL-6. Notably, the impact of IL-6 on inflammation is contextual in nature and dependent on the cell type, cytokine milieu and tissue. Targeting the IL-6/IL-6R axis in humans has been shown to successfully ameliorate a subset of autoimmune conditions. In this review, we discuss recent studies investigating how IL-6 regulates th...
Source: Current Opinion in Immunology - September 21, 2018 Category: Allergy & Immunology Authors: Jones BE, Maerz MD, Buckner JH Tags: Curr Opin Immunol Source Type: research

Emerging areas for therapeutic discovery in SLE.
Abstract Recent advances in the field of autoimmunity have identified numerous dysfunctional pathways in Systemic Lupus Erythematosus (SLE), including aberrant clearance of nucleic-acid-containing debris and immune complexes, excessive innate immune activation leading to overactive type I IFN signalling, and abnormal B and T cell activation. On the background of genetic polymorphisms that reset thresholds for immune responses, multiple immune cells contribute to inflammatory amplification circuits. Neutrophils activated by immune complexes are a rich source of immunogenic nucleic acids. Identification of new B sub...
Source: Current Opinion in Immunology - September 20, 2018 Category: Allergy & Immunology Authors: Maria NI, Davidson A Tags: Curr Opin Immunol Source Type: research

Induction of innate immune memory: the role of cellular metabolism.
A, Netea MG Abstract The paradigm that only adaptive immunity can develop immunological memory has recently been challenged by studies showing that cells from the innate immune system can undergo functional reprogramming, facilitating a faster and enhanced response to secondary infections. This improved secondary response is not always specific, as it can also protect from infections caused by non-related pathogens. This has been termed innate immune memory or trained immunity. Trained immunity not only involves rewiring the intracellular immune signaling of innate immune cells, but also induces profound changes i...
Source: Current Opinion in Immunology - September 18, 2018 Category: Allergy & Immunology Authors: Domínguez-Andrés J, Joosten LA, Netea MG Tags: Curr Opin Immunol Source Type: research

Modulation of the gut microbiota to improve innate resistance.
Abstract One major benefit from the association of hosts with the complex microbial communities that establish at body surfaces is the resistance to pathogen infection. This protective role of symbiotic microbes is becoming ever more relevant, given the alarming rise of multidrug-resistant pathogens and severe infections in patients following extensive antibiotic treatment. Herein, we highlight some recent mechanistic studies that have provided insights into how the highly dynamic dialogue amongst intestinal bacteria and between intestinal bacteria and their host can contribute to protect the host against pathogen...
Source: Current Opinion in Immunology - September 8, 2018 Category: Allergy & Immunology Authors: Schnupf P, Gaboriau-Routhiau V, Cerf-Bensussan N Tags: Curr Opin Immunol Source Type: research

When designing vaccines, consider the starting material: the human B cell repertoire.
Abstract Most viral vaccines provide protection from infection through the generation of neutralizing antibodies (nAbs). The repertoire of B cells responding to immunization is the starting material from which nAbs eventually arise. Immunization strategies are increasingly targeting precise B cell specificities to mimic nAbs generated during natural infection, in an effort to maximize the potency of the vaccine-elicited Ab response. An understanding of the human B cell specificities capable of immunogen recognition can aid in immunogen design and inform decision-making for clinical advancement. Here, we review wha...
Source: Current Opinion in Immunology - September 3, 2018 Category: Allergy & Immunology Authors: Havenar-Daughton C, Abbott RK, Schief WR, Crotty S Tags: Curr Opin Immunol Source Type: research

Loss of sterol metabolic homeostasis triggers inflammasomes  - how and why.
Loss of sterol metabolic homeostasis triggers inflammasomes - how and why. Curr Opin Immunol. 2018 Aug 29;56:1-9 Authors: Dang EV, Cyster JG Abstract Proper regulation of sterol biosynthesis is critical for eukaryotic cellular homeostasis. Cholesterol and isoprenoids serve key roles in eukaryotic cells by regulating membrane fluidity and correct localization of proteins. It is becoming increasingly appreciated that dysregulated sterol metabolism engages pathways that lead to inflammation. Of particular importance are inflammasomes, which are multiplatform protein complexes that activate ...
Source: Current Opinion in Immunology - August 29, 2018 Category: Allergy & Immunology Authors: Dang EV, Cyster JG Tags: Curr Opin Immunol Source Type: research

Harnessing CRISPR to combat human viral infections.
Abstract CRISPR/Cas9 is a technology that allows for targeted and precise genome editing in eukaryotic cells. The technique has changed the landscape of molecular biology and may be applied to repair genetic disorders in future therapies. Besides targeting the human genome, it can be used to cleave and edit viral DNA present in infected cells, and as such provides a promising new strategy for anti-viral therapy. Here, we discuss recent studies on the use of anti-viral CRISPRs to target pathogenic human viruses, with a focus on in vivo studies, challenges, and potential for future clinical applications. PMID: ...
Source: Current Opinion in Immunology - July 26, 2018 Category: Allergy & Immunology Authors: de Buhr H, Lebbink RJ Tags: Curr Opin Immunol Source Type: research

New perspectives on the initiation of allergic immune responses at barrier sites.
Abstract Although allergies exert a devastating global impact and often lack effective treatment strategies, our knowledge on the mechanisms that initiate and propagate type-2 immune responses remain enigmatic. Recent advances have highlighted additional roles for epithelial cells (e.g. tuft cells) and sensory neurons as initiators and amplifiers of type-2 immune responses. In response to protease activity of allergens, Toll-like receptor stimulation or cellular damage, these type-2 sentinels can release cytokines, alarmins or neuropeptides capable of (i) activating and expanding innate immune cells, (ii) polarizi...
Source: Current Opinion in Immunology - July 18, 2018 Category: Allergy & Immunology Authors: Noti M Tags: Curr Opin Immunol Source Type: research

Regulation of neutrophils in type 2 immune responses.
Abstract Type 2 immune responses contribute to the resistance to helminths and toxins as well as several physiological processes. Although they usually do not participate in type 2 immune responses, neutrophils have been shown in mice to enhance the anti-helminth response, but they also contribute to increased target tissue damage. Increased pathology and morbidity is also observed in type 2 immune-mediated disorders, such as allergic asthma, when neutrophils become a predominant subset of the infiltrate. How neutrophil recruitment is regulated during type 2 immune responses is now starting to become clear, with r...
Source: Current Opinion in Immunology - July 13, 2018 Category: Allergy & Immunology Authors: Heeb LEM, Egholm C, Impellizzieri D, Ridder F, Boyman O Tags: Curr Opin Immunol Source Type: research

Antiviral RNA interference in mammals.
Abstract Infection of plants and insects with RNA and DNA viruses triggers Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs), which subsequently guide specific virus clearance by RNA interference (RNAi). Consistent with a major antiviral function of RNAi, productive virus infection in these eukaryotic hosts depends on the expression of virus-encoded suppressors of RNAi (VSRs). The eukaryotic RNAi pathway is highly conserved, particularly between insects and mammals. This review will discuss key recent findings that indicate a natural antiviral function of the RNAi pathway in mammalian ce...
Source: Current Opinion in Immunology - July 12, 2018 Category: Allergy & Immunology Authors: Ding SW, Han Q, Wang J, Li WX Tags: Curr Opin Immunol Source Type: research

The hygiene hypothesis: immunological mechanisms of airway tolerance.
Abstract The hygiene hypothesis was initially proposed as an explanation for the alarming rise in allergy prevalence in the last century. The immunological idea behind this hypothesis was a lack of infections associated with a Western lifestyle and a consequential reduction in type 1 immune responses. It is now understood that the development of tolerance to allergens depends on microbial colonization and immunostimulatory environmental signals during early-life or passed on by the mother. These environmental cues are sensed and integrated by barrier epithelial cells of the lungs and possibly skin, which in turn i...
Source: Current Opinion in Immunology - July 6, 2018 Category: Allergy & Immunology Authors: Haspeslagh E, Heyndrickx I, Hammad H, Lambrecht BN Tags: Curr Opin Immunol Source Type: research

Partners in anti-crime: how interferon-inducible GTPases and autophagy proteins team up in cell-intrinsic host defense.
Abstract Once pathogens have breached the mechanical barriers to infection, survived extracellular immunity and successfully invaded host cells, cell-intrinsic immunity becomes the last line of defense to protect the mammalian host against viruses, bacteria, fungi and protozoa. Many cell-intrinsic defense programs act as high-precision weapons that specifically target intracellular microbes or cytoplasmic sites of microbial replication while leaving endogenous organelles unharmed. Critical executioners of cell-autonomous immunity include interferon-inducible dynamin-like GTPases and autophagy proteins, which often...
Source: Current Opinion in Immunology - July 5, 2018 Category: Allergy & Immunology Authors: Coers J, Brown HM, Hwang S, Taylor GA Tags: Curr Opin Immunol Source Type: research

Targeting IgE in allergic disease.
Abstract Immunoglobulin E (IgE) represents the least abundant antibody isotype in human serum. Nevertheless, it has the ability to induce potent allergic reactions. As a key component in the development and manifestation of hypersensitivity responses against usually non-hazardous foreign substances, IgE has become a major target of investigation and the subject of multiple therapeutic approaches for the treatment of allergies. Recent advances in the understanding of pathophysiologic mechanisms underlying IgE-associated allergic disorders have led to the generation of new drug candidates that are currently in devel...
Source: Current Opinion in Immunology - July 4, 2018 Category: Allergy & Immunology Authors: Gasser P, Eggel A Tags: Curr Opin Immunol Source Type: research

An update on the NLRP3 inflammasome and influenza: the road to redemption or perdition?
Abstract Inflammation is an integral aspect of influenza A virus (IAV) infection. It is critical to induce an antiviral environment to reduce viral replication and dissemination, while also being essential to the development and maturation of adaptive immunity, which ultimately resolves infection. Conversely, excessive pulmonary inflammation and cellular influx are characteristic of lethal IAV infections. It has become increasingly apparent that the innate immune inflammasome complex is a crucial moderator in IAV disease pathogenesis. It is responsible for the maturation and secretion of prototypic inflammatory cy...
Source: Current Opinion in Immunology - June 30, 2018 Category: Allergy & Immunology Authors: Michelle D T, Ashley M Tags: Curr Opin Immunol Source Type: research

Mast cells and basophils in allergic inflammation.
Abstract Mast cells and basophils have similar characteristics in terms of their function and development. They both have detrimental functions, being implicated in pro-inflammatory responses to allergens, but can also provide protection against multicellular parasites such as parasitic worms (helminths). Both cell types express the high affinity Fc receptor for IgE, FcεRI, and allergen cross-linking of this receptor triggers degranulation and release a set of cytokines and biochemical mediators. Although mast cells and basophils are similar in many respects, newly developed antibody reagents and genetical...
Source: Current Opinion in Immunology - June 28, 2018 Category: Allergy & Immunology Authors: Kubo M Tags: Curr Opin Immunol Source Type: research

Pandemic influenza vaccines: what they have taught us about B cell immunology.
Abstract The emergence of avian influenza viruses stimulated pandemic concerns and efforts to develop protective vaccines. Studies of the immune responses to experimental vaccines for pandemic influenza have taught us lessons about human immunity to influenza in general that can be applied to seasonal, pandemic, and even universal vaccine responses. For example, the concepts of targeting the hemagglutinin stalk and elicitation of stalk reactive antibodies grew out of studies of the 2009 pandemic H1N1 vaccines. More recently, the phenomenon of imprinting, the influence of early life exposure to influenza modifying ...
Source: Current Opinion in Immunology - June 26, 2018 Category: Allergy & Immunology Authors: Topham DJ, Nguyen P, Sangster MY Tags: Curr Opin Immunol Source Type: research

The structural basis for filovirus neutralization by monoclonal antibodies.
Abstract Filoviruses, including ebolaviruses and marburgviruses, are the causative agents of highly lethal disease outbreaks. The 2013-2016 Ebola virus outbreak was responsible for>28000 infections and>11000 deaths. Although there are currently no licensed vaccines or therapeutics for any filovirus-induced disease, monoclonal antibodies (mAbs) are among the most promising options for therapeutic development. Hundreds of mAbs have been isolated from human survivors of filovirus infections that target the viral spike glycoprotein (GP). The binding, neutralization, and cross-reactivity of many of these mAbs has...
Source: Current Opinion in Immunology - June 22, 2018 Category: Allergy & Immunology Authors: King LB, West BR, Schendel SL, Saphire EO Tags: Curr Opin Immunol Source Type: research

Acquired and genetic host susceptibility factors and microbial pathogenic factors that predispose to nontuberculous mycobacterial infections.
Abstract Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and human exposure is likely to be pervasive; yet, the occurrence of NTM-related diseases is relatively infrequent. This discrepancy suggests that host risk factors play an integral role in vulnerability to NTM infections. Isolated NTM lung disease (NTM-LD) is often due to underlying anatomical pulmonary or immune disorders, either of which may be acquired or genetic. However, many cases of NTM-LD have no known underlying risk factors and may be multigenic and/or multicausative. In contrast, extrapulmonary visceral or disseminated NTM dis...
Source: Current Opinion in Immunology - June 21, 2018 Category: Allergy & Immunology Authors: Honda JR, Alper S, Bai X, Chan ED Tags: Curr Opin Immunol Source Type: research

Caenorhabditis elegans in high-throughput screens for anti-infective compounds.
Abstract New classes of antimicrobials that are effective therapies for infections with multi-drug resistant pathogens are urgently needed. The nematode Caenorhabditis elegans has been incorporated into small molecule screening platforms to identify anti-infective compounds that provide protection of a host during infection. The use of a live animal in these screening systems offers several advantages, including the ability to identify molecules that boost innate immune responses in a manner advantageous to host survival and compounds that disrupt bacterial virulence mechanisms. In addition, new classes of antimic...
Source: Current Opinion in Immunology - June 20, 2018 Category: Allergy & Immunology Authors: Peterson ND, Pukkila-Worley R Tags: Curr Opin Immunol Source Type: research

Cytokine modulation of atopic itch.
Abstract Atopic dermatitis (AD) is an inflammatory skin disease characterized by two primary features: relapsing skin lesions and chronic itch. Major advances in our understanding of type 2 immunity have led to new insights into the critical factors that promote the development and persistence of AD-associated skin inflammation. Although inflammation is strongly associated with the development of atopic itch, the precise mechanisms by which itch arises in AD are poorly understood. In this review, we highlight recent studies that have started to unveil how various proinflammatory factors released within the skin ca...
Source: Current Opinion in Immunology - June 20, 2018 Category: Allergy & Immunology Authors: Trier AM, Kim BS Tags: Curr Opin Immunol Source Type: research

The causes and consequences of variation in human cytokine production in health.
Abstract Cytokines are important cell-signaling molecules that activate and modulate immune responses. Major factors influencing cytokine variation in healthy individuals are host genetics, non-heritable factors and the microbiome. Genetic variation accounts for a significant part of heterogeneity in cytokine production by peripheral blood mononuclear cells. Variation in cytokines such as IL-6 and IL-6Ra is strongly influenced by heritability, suggesting an evolutionarily pressure for their genetic regulation that potentially contributes to differences in immune responsiveness between human populations. Non-herita...
Source: Current Opinion in Immunology - June 15, 2018 Category: Allergy & Immunology Authors: Schirmer M, Kumar V, Netea MG, Xavier RJ Tags: Curr Opin Immunol Source Type: research

The widening spectrum of immunological memory.
Abstract Immunological memory is broadly understood as the underlying mechanism by which an organism remembers previous encounters with pathogens, aberrant cells, or self-antigens to produce a more rapid or robust secondary response upon re-encounter. This phenomenon is widely accepted as the hallmark feature of the adaptive immune system. However, work within the last decade has continuously challenged this viewpoint and opened up the idea that immunological memory extends beyond just conventional B cells and T cells. Along with critical studies on natural killer cells, recent evidence suggest that innate B and T...
Source: Current Opinion in Immunology - June 11, 2018 Category: Allergy & Immunology Authors: Lau CM, Sun JC Tags: Curr Opin Immunol Source Type: research

Harnessing immune history to combat influenza viruses.
Abstract Individuals are exposed to influenza viruses throughout their lifetime. Accumulating evidence shows the first viruses an individual is exposed to leaves an imprint on the antibody response induced by subsequent drifted and novel influenza viral exposures. Imprinted humoral immunity against influenza viruses relies on biased immune memory to influenza viruses for which memory B cell responses were initially generated against. Imprinting allows for antibodies to adapt to drifted influenza viruses while maintaining binding potential for the first influenza viruses an individual is exposed to. However, imprin...
Source: Current Opinion in Immunology - June 8, 2018 Category: Allergy & Immunology Authors: Guthmiller JJ, Wilson PC Tags: Curr Opin Immunol Source Type: research

Crosstalk between type I and II interferons in regulation of myeloid cell responses during bacterial infection.
Abstract Type I and type II interferons (IFNα/β and IFNγ) are cytokines that play indispensable roles in directing myeloid cell activity during inflammatory and immune responses. Each IFN type binds a distinct receptor (IFNAR or IFNGR) to transduce signals that reshape gene expression and function of myeloid and other cell types. In the context of murine models and human bacterial infections, production of IFNγ generally promotes resistance while production of IFNα/β is associated with increased host susceptibility. Here, we review mechanisms of crosstalk between type I and II IFN...
Source: Current Opinion in Immunology - June 7, 2018 Category: Allergy & Immunology Authors: Crisler WJ, Lenz LL Tags: Curr Opin Immunol Source Type: research

Role of neutrophils in allergic asthma.
Abstract The contribution of neutrophils to asthma pathogenesis has been mainly studied in the context of non-allergic neutrophilic asthma. However, neutrophils can also be rapidly recruited and are largely present in the airways of allergic eosinophilic asthmatic patients. Under these circumstances, they possess specific phenotypic features distinguishing them from resting blood neutrophils and are endowed with particular functions. The exact contribution of neutrophils to allergic asthma pathogenesis is still unclear, but growing experimental evidence supports the ability of neutrophils or neutrophil-derived pro...
Source: Current Opinion in Immunology - June 5, 2018 Category: Allergy & Immunology Authors: Radermecker C, Louis R, Bureau F, Marichal T Tags: Curr Opin Immunol Source Type: research

Dendritic cells in inflammatory angiogenesis and lymphangiogenesis.
Abstract Lymph node (LN) expansion during inflammation is essential to establish immune responses and relies on the development of blood and lymph vessels. Human dendritic cells (DCs), subdivided into two main subsets, namely conventional DCs (cDCs) and plasmacytoid DCs (pDCs), are professional antigen presenting cells endowed with the capability to produce soluble mediators regulating inflammation and tissue repair. cDCs support angiogenesis in secondary LNs both directly and indirectly through the secretion of vascular endothelial growth factor-A (VEGF)-A and VEGF-C and the production of several other mediators ...
Source: Current Opinion in Immunology - June 4, 2018 Category: Allergy & Immunology Authors: Bosisio D, Ronca R, Salvi V, Presta M, Sozzani S Tags: Curr Opin Immunol Source Type: research