A three course menu for ILC and bystander T cell activation.
Abstract The varied list of agonists that activate innate lymphoid cells (ILCs) continues to grow, but whether and how these signals interact is not well defined, especially in vivo. ILC subsets share master transcription factors, chromatin landscapes, and effector cytokines with their corresponding T helper (Th) cell subsets. Here we discuss how studies of these two cell types can inform each other. Specifically, we outline a framework in which ILC agonists are grouped by the transcription factors they activate. Optimal ILC activation requires at least three items from a 'menu' of non-redundant signals that colle...
Source: Current Opinion in Immunology - December 9, 2019 Category: Allergy & Immunology Authors: McGinty JW, von Moltke J Tags: Curr Opin Immunol Source Type: research

Sense and immuno-sensibility: innate lymphoid cell niches and circuits.
Abstract Tissue-resident lymphocytes that lack expression of rearranged antigen receptors and are lineage negative for classical T and B cell markers are collectively known as innate lymphoid cells (ILCs). The ILC family is remarkably heterogeneous and exhibits plasticity; however, mature ILCs can be grouped based on their steady state expression of distinct surface receptors and transcription factors as well as production of signature cytokines following activation. The study of ILC subsets in mouse and human tissues has revealed that the elicitation and magnitude of their effector functions are determined by a c...
Source: Current Opinion in Immunology - December 8, 2019 Category: Allergy & Immunology Authors: McFarland AP, Colonna M Tags: Curr Opin Immunol Source Type: research

Complexity and heterogeneity - the defining features of autoimmune disease.
PMID: 31813416 [PubMed - in process] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - December 1, 2019 Category: Allergy & Immunology Authors: Sanz I, Lund F Tags: Curr Opin Immunol Source Type: research

Metabolic control of B cell immune responses.
Abstract Humoral immunity critically depends on appropriate B cell responses. B cell activation, proliferation, differentiation and antibody secretion are processes carefully orchestrated by a complex network of intracellular signaling pathways and transcription factors. In order to meet the energetic and biosynthetic demands of protein synthesis and cell division, signal transduction pathways reshape the metabolic profile of activated B cells. However, the relationship between signaling and metabolism is by no means unidirectional. Emerging evidence suggests that shifts in available fuel sources and intracellular...
Source: Current Opinion in Immunology - November 30, 2019 Category: Allergy & Immunology Authors: Jellusova J Tags: Curr Opin Immunol Source Type: research

New insights on T-cell self-tolerance.
Abstract Self-tolerance of T cells is maintained by a combination of thymic negative selection and suppression by T regulatory cells (Tregs); both processes are driven by recognition of self MHC ligands. Treg function ensures that most T cells remain quiescent as naïve cells, but enables some T cells to proliferate and differentiate into cells with a memory phenotype (MP). In this review, we discuss how Tregs shape this compartmentalization of T cells into subsets of naïve and MP T cells. PMID: 31786417 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - November 28, 2019 Category: Allergy & Immunology Authors: Yi J, Kawabe T, Sprent J Tags: Curr Opin Immunol Source Type: research

New function of zebrafish regulatory T cells in organ regeneration.
Abstract Zebrafish can efficiently regenerate complex tissue structures with a highly developed innate and adaptive immune system, which provides a model to investigate the roles of immune cells in tissue repair and regeneration. Two groups recently reported zebrafish mutants deficient in a forkhead box P3 (FOXP3) ortholog, which helped reveal the conserved immunosuppressive function of zebrafish FOXP3 in vivo. Zebrafish FOXP3 defines the development of a subset of T cell lineage with the conserved gene expression profile of mammalian regulatory T cells (Tregs). In damaged organs, zebrafish Tregs rapidly migrate t...
Source: Current Opinion in Immunology - November 22, 2019 Category: Allergy & Immunology Authors: Kikuchi K Tags: Curr Opin Immunol Source Type: research

B cell targeted therapies in autoimmune disease.
Abstract PURPOSE OF REVIEW: FDA-approved B cell-targeted therapy has expanded to a multitude of autoimmune diseases ranging from organ specific diseases, like pemphigus and multiple sclerosis, to systemic diseases such as ANCA-associated vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this review, we discuss the variability in response to B cell-targeted therapies with a focus on the diversity of human B cells and plasma cells, and will discuss several of the promising new B cell-targeted therapies. RECENT FINDING: The pathogenic roles for B cells include autoantibody-dependen...
Source: Current Opinion in Immunology - November 13, 2019 Category: Allergy & Immunology Authors: Barnas JL, Looney RJ, Anolik JH Tags: Curr Opin Immunol Source Type: research

Pathogenic memory plasma cells in autoimmunity.
h A PMID: 31675681 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 29, 2019 Category: Allergy & Immunology Authors: Chang HD, Tokoyoda K, Hoyer B, Alexander T, Khodadadi L, Mei H, Dörner T, Hiepe F, Burmester GR, Radbruch A Tags: Curr Opin Immunol Source Type: research

Macrophage ontogeny in the control of adipose tissue biology.
Abstract Macrophages are found in large numbers in the adipose tissue where they closely associate with the adipocytes and the vasculature. Adipose tissue macrophages are a heterogenous population of cells with 'hard wired' diversity brought upon by distinct developmental lineages. The purpose of this review is to provide a brief history of macrophages in control of adipose tissue metabolism with the emphasis on the importance of macrophage ontogeny. PMID: 31670115 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 25, 2019 Category: Allergy & Immunology Authors: Cox N, Geissmann F Tags: Curr Opin Immunol Source Type: research

IgM memory B cells: specific effectors of innate-like and adaptive responses.
Abstract Antigen-experienced IgM+ B cells with mutated V genes have emerged as important effectors of both adaptive and innate-like immune responses. While their precise role in recall responses appear to differ according to the nature of the immunogen or the infectious agent, they are able to achieve rapid plasma cell differentiation, germinal center re-initiation, as well as IgM and IgG memory pool replenishment, which establishes them as multi-lineage precursors of the various functional memory subsets. For innate-like responses, recent data have shown that activation by gut commensals is able to generate, both...
Source: Current Opinion in Immunology - October 19, 2019 Category: Allergy & Immunology Authors: Weill JC, Reynaud CA Tags: Curr Opin Immunol Source Type: research

Systemic Lupus Erythematosus and dysbiosis in the microbiome: cause or effect or both?
Abstract Throughout our lives we are immersed in, and colonized by, immense and complex microbial communities. These microbiota serve as activators and early sparring partners for the progressive construction of the layers within our immune defenses and are essential to immune homeostasis. Yet, at times imbalances within the microbiota may contribute to metabolic and immune regulatory abnormalities that underlie the development of inflammatory and autoimmune diseases. Here, we review recent progress in investigations of the microbiome, with emphasis on the gut microbiota associated with systemic autoimmunity. In p...
Source: Current Opinion in Immunology - October 4, 2019 Category: Allergy & Immunology Authors: Silverman GJ, Azzouz DF, Alekseyenko AV Tags: Curr Opin Immunol Source Type: research

The role of nucleic acid sensors and type I IFNs in patient populations and animal models of autoinflammation.
n A Abstract A spectrum of human autoinflammatory conditions result from defects in cytosolic nucleic acid clearance or overexpression of the nucleic acid sensor STING. These patients often develop severely debilitating lesions and invariably show robust IFN signatures that have been attributed to the cGAS/STING signaling cascade and type I IFN. However, murine models that recapitulate major features of these syndromes have now shown that autoinflammation is more likely to depend on type II IFN/IFNgamma or type III IFN/IFNlambda, and further revealed a critical role for Th1 cells in tissue damage and the persisten...
Source: Current Opinion in Immunology - September 27, 2019 Category: Allergy & Immunology Authors: Nündel K, Marshak-Rothstein A Tags: Curr Opin Immunol Source Type: research

On the mark: genetically engineered immunotherapies for autoimmunity.
Abstract Current therapies for autoimmunity cause significant morbidity and mortality. Adoptive immunotherapy using genetically engineered T cells has led to durable remissions of B cell leukemias and lymphomas, raising the question of whether the approach can be modified to target autoreactive B and T cells to induce durable remissions of autoimmunity. Here we review antigen-specific approaches to modify immune cells to treat autoimmune disease. We focus on recent studies that aim to eliminate or suppress autoimmunity by targeting the disease-causing B or T cells through their B cell receptor or T cell receptor s...
Source: Current Opinion in Immunology - September 26, 2019 Category: Allergy & Immunology Authors: Ellebrecht CT, Lundgren DK, Payne AS Tags: Curr Opin Immunol Source Type: research

Autoimmune complications of cancer immunotherapy.
Abstract Immunotherapy of cancer with blockade of inhibitory immune checkpoints and adoptive cell therapies have led to impressive clinical responses in several cancers. However, with increasing utilization of these therapies, immune-related adverse events have emerged as a major obstacle. Herein I discuss recent insights into the immunobiology of these toxicities. Deeper understanding of the underlying pathogenic mechanisms, cellular and molecular pathways involved, similarities and differences with spontaneous autoimmunity, and identification of clinically relevant predictive biomarkers is needed to develop opti...
Source: Current Opinion in Immunology - September 23, 2019 Category: Allergy & Immunology Authors: Dhodapkar KM Tags: Curr Opin Immunol Source Type: research

Shared and unique immune alterations in pre-clinical autoimmunity.
Abstract Progression from health to a classified autoimmune disease is an evolving process that can happen rapidly in some diseases, but usually takes years to develop. Specific immune alterations predate pathogenic autoimmunity and can be used as disease biomarkers to identify high-risk individuals for prevention studies applied in the pre-clinical state. Here we discuss recent findings that illuminate specific immune pathways that are altered in the earliest phases of pre-clinical autoimmunity as well as those mediators more closely associated with later clinically apparent and classified disease onset. PMI...
Source: Current Opinion in Immunology - September 23, 2019 Category: Allergy & Immunology Authors: Slight-Webb S, Bourn RL, Holers VM, James JA Tags: Curr Opin Immunol Source Type: research

How a farming environment protects from atopy.
Abstract It is now well established that the exposure to certain environments such as farms has the potential to protect from the development of allergies later in life. This protection is achieved when repeated exposure to the farming environment occurs early in life, but persists when children spend sufficient amount of time in contact with livestock and hay, and drink unpasteurized milk. The capacity of farm dust to protect from allergy development lies, amongst others, in the microbe composition in the farm. These protective microbes release various metabolites and cell wall components that change farmers' hom...
Source: Current Opinion in Immunology - September 6, 2019 Category: Allergy & Immunology Authors: Deckers J, Lambrecht BN, Hammad H Tags: Curr Opin Immunol Source Type: research

Antigen-specific tolerance to self-antigens in protein replacement therapy, gene therapy and autoimmunity.
Abstract Trials of antigen-specific tolerance have been undertaken in the clinic for over fifty years and the results of these antigen-specific clinical trials are described in this review. Antigen-specific tolerization of the immune system in protein replacement therapy for hemophilia A is an accepted treatment. Clinical trials are ongoing for autoimmune conditions such as type 1 diabetes, multiple sclerosis, neuromyelitis optica, and rheumatoid arthritis with various antigen-specific strategies. Trials for tolerization in celiac disease aim for antigen specific tolerance to gluten, an environmental trigger, whic...
Source: Current Opinion in Immunology - August 30, 2019 Category: Allergy & Immunology Authors: Steinman L, Ho PP, Robinson WH, Utz PJ, Villoslada P Tags: Curr Opin Immunol Source Type: research

Editorial overview: Attrition warfare: host cell weapons against intracellular pathogens, and how the pathogens fight back.
PMID: 31471114 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 27, 2019 Category: Allergy & Immunology Authors: Stallings CL, Glickman MS Tags: Curr Opin Immunol Source Type: research

Interactions between environmental pollutants and genetic susceptibility in asthma risk.
Abstract Exposure to air pollution is associated with enhanced risk of developing asthma, notably in the presence of genetic risk factors. Interaction analyses have shown that both outdoor and indoor air pollution interact with genetic variability to increase the incidence of asthma. In this review, we summarize recent progress in candidate gene-based studies, as well as genome-wide gene-air pollution interaction studies. Advances in epigenetics have provided evidence for DNA methylation as a mediator in gene-air pollution interactions. Emerging strategies for study design and statistical analyses may improve powe...
Source: Current Opinion in Immunology - August 27, 2019 Category: Allergy & Immunology Authors: Johansson H, Mersha TB, Brandt EB, Khurana Hershey GK Tags: Curr Opin Immunol Source Type: research

Mechanisms of action of low-dose IL-2 restoration therapies in SLE.
Abstract Interleukin-2 (IL-2) shortage is a hallmark of Systemic Lupus Erythematosus (SLE). Importantly, clinical and preclinical studies demonstrate the potential clinical benefits of IL-2-based restoration therapies for the treatment of SLE. Here we discuss the immunological consequences of IL-2 deficiency in SLE patients and the mechanisms underlying the therapeutic effects of low-dose IL-2 regimens. PMID: 31450016 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 23, 2019 Category: Allergy & Immunology Authors: Ballesteros-Tato A, Papillion A Tags: Curr Opin Immunol Source Type: research

Human monoclonal antibodies for discovery, therapy, and vaccine acceleration.
Abstract Screening of single B cells from convalescent or vaccinated people allows the discovery of novel targets for infectious diseases and rapid production of engineered human monoclonal antibodies (mAbs) that can prevent or control infections by passive immunization. Here we propose that the development of human mAbs can also significantly accelerate vaccine development by anticipating some of the key biological and regulatory questions. PMID: 31450054 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 23, 2019 Category: Allergy & Immunology Authors: Andreano E, Seubert A, Rappuoli R Tags: Curr Opin Immunol Source Type: research

Molecular pattern recognition in peripheral B cell tolerance: lessons from age-associated B cells.
Abstract Although central tolerance mechanisms purge self-reactive B cells during development based on BCR signal strength, mechanisms that block the differentiation of autoreactive effector and memory B cells from mature pools remain poorly understood. Prior observations implicate nucleic acid sensing TLRs in autoimmunity, and more recent findings show that TLR9 is also involved in maintaining peripheral tolerance. Studies of the immunological changes that occur during aging revealed a subset of B cells denoted Age-associated B cells which expands in settings of aging and in autoimmunity. Further studies demonstr...
Source: Current Opinion in Immunology - August 22, 2019 Category: Allergy & Immunology Authors: Johnson JL, Scholz JL, Marshak-Rothstein A, Cancro MP Tags: Curr Opin Immunol Source Type: research

Understanding regulatory B cells in autoimmune diseases: the case of multiple sclerosis.
Abstract The suppressive function of B cells is mediated mostly through their provision of cytokines with anti-inflammatory properties, in particular interleukin-10. This B cell activity has been convincingly described in mice with autoimmune, infectious, as well as malignant diseases, and evidence is accumulating of its relevance in human. This review provides a personal view of this B cell function using multiple sclerosis and its animal model experimental autoimmune encephalomyelitis as representative examples, in an attempt to bridge observations obtained in mice and human, with the goal of providing a coheren...
Source: Current Opinion in Immunology - August 21, 2019 Category: Allergy & Immunology Authors: Thi Cuc B, Pohar J, Fillatreau S Tags: Curr Opin Immunol Source Type: research

Capturing the antigen landscape: HLA-E, CD1 and MR1.
Abstract T cell receptor (TCR) recognition of antigens presented by relatively non-polymorphic MHC-like molecules is emerging as a significant contributor to health and disease. These evolutionarily ancient pathways have been inappropriately labelled 'non-conventional' because their roles were discovered after viral-specific peptide presentation by polymorphic MHC class I molecules. We suggest that these pathways are complementary to mainstream peptide presentation. HLA-E, CD1 and MR1 can present diverse self and foreign antigens to TCRs and therefore contribute to tissue homeostasis, pathogen defence, inflammatio...
Source: Current Opinion in Immunology - August 21, 2019 Category: Allergy & Immunology Authors: Ogg G, Cerundolo V, McMichael AJ Tags: Curr Opin Immunol Source Type: research

Roles for the adaptive immune system in Parkinson's and Alzheimer's diseases.
Abstract Neurodegenerative diseases, such as Parkinson's and Alzheimer's, affect millions of people and pose major personal and socioeconomic burdens. The causes of neurodegeneration are mostly unknown, although current efforts have described an autoimmune aspect to these diseases. Here we discuss recent findings that shed light on the involvement of the adaptive immune system in Parkinson's and Alzheimer's diseases, and provide a model and outlook for further investigation of T cell responses in neurodegenerative disease. We focus on the identification of T cell epitopes from proteins involved in disease pathogen...
Source: Current Opinion in Immunology - August 17, 2019 Category: Allergy & Immunology Authors: Lindestam Arlehamn CS, Garretti F, Sulzer D, Sette A Tags: Curr Opin Immunol Source Type: research

Multimodal single-cell approaches shed light on T cell heterogeneity.
Abstract Single-cell methods have revolutionized the study of T cell biology by enabling the identification and characterization of individual cells. This has led to a deeper understanding of T cell heterogeneity by generating functionally relevant measurements - like gene expression, surface markers, chromatin accessibility, T cell receptor sequences - in individual cells. While these methods are independently valuable, they can be augmented when applied jointly, either on separate cells from the same sample or on the same cells. Multimodal approaches are already being deployed to characterize T cells in diverse ...
Source: Current Opinion in Immunology - August 17, 2019 Category: Allergy & Immunology Authors: Nathan A, Baglaenko Y, Fonseka CY, Beynor JI, Raychaudhuri S Tags: Curr Opin Immunol Source Type: research

Metabolic regulation of pathogenic autoimmunity: therapeutic targeting.
Abstract Metabolism has recently emerged as an essential mechanism that regulates the immune system. Studies in healthy mice and, to a lesser extent, humans, have defined the metabolism of immune cells in response to various challenges. It is increasingly recognized that the overactive immune system that drives autoimmune diseases presents metabolic abnormalities that offer therapeutic opportunities. These novel therapeutic venues are supported by a few studies using metabolic inhibitors in mouse models and in small clinical trials. Reaching the full potential of targeting immuno-metabolism in autoimmune diseases ...
Source: Current Opinion in Immunology - August 15, 2019 Category: Allergy & Immunology Authors: Teng X, Cornaby C, Li W, Morel L Tags: Curr Opin Immunol Source Type: research

Spatial and functional heterogeneity of follicular helper T cells in autoimmunity.
Abstract Follicular helper T cells provide signals that promote B cell development, proliferation, and production of affinity matured and appropriately isotype switched antibodies. In addition to their classical locations within B cell follicles and germinal centers therein, B cell helper T cells are also found in extrafollicular spaces - either in secondary lymphoid or non-lymphoid tissues. Both follicular and extrafollicular T helper cells drive autoantibody-mediated autoimmunity. Interfering with B cell help provided by T cells can ameliorate autoimmune disease in animal models and human patients. The next fron...
Source: Current Opinion in Immunology - July 30, 2019 Category: Allergy & Immunology Authors: Seth A, Craft J Tags: Curr Opin Immunol Source Type: research

Recent progress in the analysis of αβT cell and B cell receptor repertoires.
Recent progress in the analysis of αβT cell and B cell receptor repertoires. Curr Opin Immunol. 2019 Jul 17;59:109-114 Authors: Davis MM, Boyd SD Abstract T cell receptors (TCRs) and B cell receptors (BCRs) are vertebrate evolution's best answer to the threat of microbial pathogens that can evolve much faster than ourselves. These antigen receptors are generated during T cell or B cell development by combinatorial rearrangement of germline genome V, D and J gene segments, and with junctional residues capable of enormous diversity. For decades the complexity of these receptor repertoires has...
Source: Current Opinion in Immunology - July 17, 2019 Category: Allergy & Immunology Authors: Davis MM, Boyd SD Tags: Curr Opin Immunol Source Type: research

Regulation of oral immune tolerance by the microbiome in food allergy.
Abstract The steep rise in the incidence and prevalence of food allergy (FA) in the last few decades have focused attention of environmental mechanisms which act to promote disease, chief among which is the microbiome. Recent studies have now established the presence of pathogenic dysbiosis in FA that could be precipitated by a variety of environmental insults, including among others antibiotic usage and mode of delivery, that act to subvert the immune regulatory response that enforce tolerance to dietary antigens. A key attribute of this dysbiosis is the loss of Clostridial bacterial species that act to promote t...
Source: Current Opinion in Immunology - July 11, 2019 Category: Allergy & Immunology Authors: Stephen-Victor E, Chatila TA Tags: Curr Opin Immunol Source Type: research

Gene-environment interactions in primary atopic disorders.
Abstract Environmental factors modify disease presentation and severity in allergic disorders. Primary atopic disorders (PADs) are a heterogenous group of single gene disorders that lead to significant atopic and allergic disease manifestations. However, a number of these monogenic diseases have variable penetrance suggesting that gene-gene and/or gene-environment interactions could modulate the clinical phenotype. Environmental factors such as diet, the microbiome at the epithelial-environment interface, the presence and/or extent of infection, and psychologic stress can alter disease phenotypic expression of all...
Source: Current Opinion in Immunology - July 11, 2019 Category: Allergy & Immunology Authors: Sacco KA, Milner JD Tags: Curr Opin Immunol Source Type: research

Cell intrinsic functions of neutrophils and their manipulation by pathogens.
Abstract Neutrophils are a crucial first line of defense against infection, migrating rapidly into tissues where they deploy granule components and toxic oxidants for efficient phagocytosis and microbe killing. Subsequent apoptosis and clearance of dying neutrophils are essential for control of infection and resolution of the inflammatory response. A subset of microbial pathogens survive exposure to neutrophils by manipulating phagocytosis, phagosome-granule fusion, oxidant production, and lifespan. Elucidating how they accomplish this unusual feat provides new insights into normal neutrophil function. In this rev...
Source: Current Opinion in Immunology - July 10, 2019 Category: Allergy & Immunology Authors: Allen LH, Criss AK Tags: Curr Opin Immunol Source Type: research

The phagocyte NOX2 NADPH oxidase in microbial killing and cell signaling.
Abstract The phagocyte NADPH oxidase possesses a transmembrane electron transferase comprised of gp91phox (aka NOX2) and p22phox and two multicomponent cytosolic complexes, which in stimulated phagocytes translocate to assemble a functional enzyme complex at plasma or phagosomal membranes. The NOX2-centered NADPH oxidase shuttles electrons from cytoplasmic NADPH to molecular oxygen in phagosomes or the extracellular space to produce oxidants that support optimal antimicrobial activity by phagocytes. Additionally, NOX2-generated oxidants have been implicated in both autocrine and paracrine signaling in a variety of...
Source: Current Opinion in Immunology - July 10, 2019 Category: Allergy & Immunology Authors: Nauseef WM Tags: Curr Opin Immunol Source Type: research

Human lung tissue resident memory T cells in health and disease.
Abstract The human lung contains a heterogeneous population of immune cells which mediate protective responses, maintain tissue homeostasis, but can also promote immunopathology in disease. The majority of T cells in the human lung are tissue resident memory T cells (TRM) which have been shown in mouse models to provide vital roles in the protection against multiple respiratory pathogens, and contribute to heterosubtypic protection in the context of vaccination. In this review, we will discuss recent studies in humans identifying lung TRM, their role in maintaining tissue homeostasis, and emerging evidence implica...
Source: Current Opinion in Immunology - June 29, 2019 Category: Allergy & Immunology Authors: Snyder ME, Farber DL Tags: Curr Opin Immunol Source Type: research

Metabolic reprogramming: an innate cellular defence mechanism against intracellular bacteria?
Abstract The limited metabolic resources of a cell represent an intriguing 'conflict of interest' during host-pathogen interactions, as the battle for nutrients might determine the outcome of an infection. To adapt their metabolic needs, innate immune cells such as monocytes, macrophages or dendritic cells reprogram their metabolism upon activation by microbial compounds. In turn, infection by intracellular bacteria provokes metabolic alterations of the host cell that benefit the pathogen. Here, we discuss the state-of-the-art knowledge on metabolic reprogramming of host cells upon activation or infection with int...
Source: Current Opinion in Immunology - June 24, 2019 Category: Allergy & Immunology Authors: Escoll P, Buchrieser C Tags: Curr Opin Immunol Source Type: research

LC3-associated phagocytosis: host defense and microbial response.
Abstract The innate immune system has evolved to recognize diverse microbes and destroy them. At the same time, microbial pathogens undermine immunity to cause disease. Here, we highlight recent advances in understanding an antimicrobial pathway called LC3-associated phagocytosis (LAP), which combines features of autophagy with phagocytosis. Upon phagocytosis, many microbes, including bacteria, fungi, and parasites, are sequestered in an LC3-positive, single-membrane bound compartment, a hallmark of LAP. LAP depends upon NADPH oxidase activity at the incipient phagosome and culminates in lysosomal trafficking and ...
Source: Current Opinion in Immunology - June 24, 2019 Category: Allergy & Immunology Authors: Upadhyay S, Philips JA Tags: Curr Opin Immunol Source Type: research

Editorial overview: Vaccine immunology: what is seen and not seen.
PMID: 31235312 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 21, 2019 Category: Allergy & Immunology Authors: Crotty S Tags: Curr Opin Immunol Source Type: research

HIF-1 α as a central mediator of cellular resistance to intracellular pathogens.
HIF-1α as a central mediator of cellular resistance to intracellular pathogens. Curr Opin Immunol. 2019 Jun 20;60:111-116 Authors: Knight M, Stanley S Abstract Hypoxia-inducible transcription factor-1α (HIF-1α) was originally identified as a master regulator of cellular responses to hypoxia. More recently, HIF-1α has emerged as a critical regulator of immune cell function that couples shifts in cellular metabolism to cell type-specific transcriptional outputs. Activation of macrophages with inflammatory stimuli leads to induction of the metabolic program aerobic glycolysis and ...
Source: Current Opinion in Immunology - June 20, 2019 Category: Allergy & Immunology Authors: Knight M, Stanley S Tags: Curr Opin Immunol Source Type: research

Apoptosis inhibition by intracellular bacteria and its consequence on host immunity.
Abstract Regulated cell death via apoptosis not only is important for organismal homeostasis but also serves as an innate defense mechanism. The engulfment of apoptotic infected cells, a process known as efferocytosis, is a common pathway for the destruction of many intracellular bacteria. Some pathogens take advantage of efferocytosis to prevent activation of macrophages and thereby facilitate their dissemination. Conversely, many obligate intracellular bacterial pathogens and some facultative-intracellular bacteria inhibit apoptosis, preventing efferocytosis, and evading innate host defenses. The molecular mecha...
Source: Current Opinion in Immunology - June 19, 2019 Category: Allergy & Immunology Authors: Behar SM, Briken V Tags: Curr Opin Immunol Source Type: research

Reactive nitrogen species in host-bacterial interactions.
res A Abstract Reactive nitrogen species play diverse and essential roles in host-pathogen interactions. Here, we review selected recent discoveries regarding nitric oxide (NO) in host defense and the pathogenesis of infection, mechanisms of bacterial NO resistance, production of NO by human macrophages, NO-based antimicrobial therapeutics and NO interactions with the gut microbiota. PMID: 31200187 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 11, 2019 Category: Allergy & Immunology Authors: Fang FC, Vázquez-Torres A Tags: Curr Opin Immunol Source Type: research

Contribution of antimicrobials to the development of allergic disease.
Abstract Antimicrobials represent a broad class of chemicals with the intended purpose of eliminating or controlling the growth of harmful microorganisms. Exposure can occur occupationally or through the use or consumption of consumer products. The use of antimicrobial agents has been associated with an increased incidence of allergic diseases, including asthma, atopic dermatitis, and less commonly, anaphylaxis. Very diverse immunological mechanisms and mediators have been identified in the sensitization response to antimicrobial chemicals and the importance of the local microenviroment in the response is increasi...
Source: Current Opinion in Immunology - June 8, 2019 Category: Allergy & Immunology Authors: Anderson SE, Weatherly L, Shane HL Tags: Curr Opin Immunol Source Type: research

Heterogeneity and fate choice: T cell exhaustion in cancer and chronic infections.
Abstract CD8 T cell differentiation is a tightly regulated process generating effector and memory T cells over the course of acute infections. In cancer and chronic infection, this differentiation program is derailed, and antigen-specific CD8 T cells differentiate to a hyporesponsive state generally referred to as T cell exhaustion. Here, we review recent findings on heterogeneity of tumor-specific T cells and exhausted T cells during chronic infections, discussing distinct differentiation state dynamics, fate choices, and functional states. Delineating the regulatory mechanisms defining distinct T cell states and...
Source: Current Opinion in Immunology - June 7, 2019 Category: Allergy & Immunology Authors: Philip M, Schietinger A Tags: Curr Opin Immunol Source Type: research

Cell-autonomous immunity by IFN-induced GBPs in animals and plants.
Abstract Inside host cells, guanylate binding proteins (GBPs) rapidly assemble into large antimicrobial defense complexes that combat a wide variety of bacterial pathogens. These massive nanomachines often completely coat targeted microbes where they act as recruitment platforms for downstream effectors capable of direct bactericidal activity. GBP-containing platforms also serve as sensory hubs to activate inflammasome-driven responses in the mammalian cytosol while in plants like Arabidopsis, GBP orthologues may facilitate intranuclear signaling for immunity against invasive phytopathogens. Together, this group o...
Source: Current Opinion in Immunology - June 5, 2019 Category: Allergy & Immunology Authors: Huang S, Meng Q, Maminska A, MacMicking JD Tags: Curr Opin Immunol Source Type: research

Host inflammasome defense mechanisms and bacterial pathogen evasion strategies.
Abstract Inflammasomes are a formidable armada of intracellular pattern recognition receptors. They recognize determinants of infection, such as foreign entities or danger signals within the host cell cytosol, rapidly executing innate immune defenses and initiating adaptive immune responses. Although inflammasomes are implicated in many diseases, they are especially critical in host protection against intracellular bacterial pathogens. Given this role, it is not surprising that many pathogens have evolved effective strategies to evade inflammasome activation. In this review, we will provide a brief summary of infl...
Source: Current Opinion in Immunology - June 4, 2019 Category: Allergy & Immunology Authors: Brewer SM, Brubaker SW, Monack DM Tags: Curr Opin Immunol Source Type: research

Remembering to remember: T cell memory maintenance and plasticity.
Abstract Upon activation, naive T cells give rise to a heterogeneous cell population of effector and memory T cells that mediate antigen clearance and provide long-lived protection from rechallenge. Many of the transcriptional regulators that direct the differentiation of naive T cells to acquire the range of phenotypic and functional characteristics of effector and memory T cells have been described. However, the active programs that maintain the specific subsets of memory T cells are less clear. Here, we discuss recent studies that suggest effector and memory CD8+ T cells exist in cellular 'states' with inherent...
Source: Current Opinion in Immunology - June 3, 2019 Category: Allergy & Immunology Authors: Omilusik KD, Goldrath AW Tags: Curr Opin Immunol Source Type: research

Genetic evidence for the role of transforming growth factor- β in atopic phenotypes.
Genetic evidence for the role of transforming growth factor-β in atopic phenotypes. Curr Opin Immunol. 2019 Jun 01;60:54-62 Authors: Weissler KA, Frischmeyer-Guerrerio PA Abstract New evidence in humans and mice supports a role for transforming growth factor-β (TGF-β) in the initiation and effector phases of allergic disease, as well as in consequent tissue dysfunction. This pleiotropic cytokine can affect T cell activation and differentiation and B cell immunoglobulin class switching following initial encounter with an allergen. TGF-β can also act on mast cells during an acute all...
Source: Current Opinion in Immunology - June 1, 2019 Category: Allergy & Immunology Authors: Weissler KA, Frischmeyer-Guerrerio PA Tags: Curr Opin Immunol Source Type: research

Development, ontogeny, and maintenance of TCR αβ+ CD8αα IEL.
Development, ontogeny, and maintenance of TCRαβ+ CD8αα IEL. Curr Opin Immunol. 2019 May 27;58:83-88 Authors: Ruscher R, Hogquist KA Abstract The intestinal epithelium is the outermost cellular layer that separates the body from the gut lumen. The integrity of this protective mucosal barrier is crucial and maintained by specialized cells-intraepithelial lymphocytes (IEL). Much research has been conducted on these cells and our overall understanding of them is increasing rapidly. In this review we focus on the TCRαβ+ subset of CD8αα IEL. We discuss recent st...
Source: Current Opinion in Immunology - May 27, 2019 Category: Allergy & Immunology Authors: Ruscher R, Hogquist KA Tags: Curr Opin Immunol Source Type: research

MAIT cells: programmed in the thymus to mediate immunity within tissues.
Abstract MAIT cells are an evolutionarily conserved T cell subset recognizing ubiquitous microbial metabolites. Herein, we review recent literature showing that MAIT cells can be divided into type 1 and type 17 subsets, which acquire a tissue resident differentiation program in the thymus and localize in specific tissues. We also discuss the nature and in vivo availability of the different agonist and antagonist MAIT ligands with potential consequences for MAIT cell biology. PMID: 31141764 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 26, 2019 Category: Allergy & Immunology Authors: Lantz O, Legoux F Tags: Curr Opin Immunol Source Type: research

New players in the gene regulatory network controlling late B cell differentiation.
Abstract The differentiation of B cells into antibody-secreting plasma cells is associated with profound changes in morphology, lifespan, and cellular metabolism that are needed to support high rates of antibody production. These processes are driven by dramatic alterations to the transcriptional program and to the organization of the nucleus itself that in turn are regulated by the activity of a select group of transcription factors and epigenetic regulators. Although the core differentiation program is conserved in all mature B cells, subset-specific regulators, such as those found in B1 or memory B cells, provi...
Source: Current Opinion in Immunology - May 24, 2019 Category: Allergy & Immunology Authors: Willis SN, Nutt SL Tags: Curr Opin Immunol Source Type: research

Role of genetics, environment, and their interactions in the pathogenesis of eosinophilic esophagitis.
Abstract The rise in incidence and prevalence of eosinophilic esophagitis (EoE) since the 1990s has prompted investigations into its pathogenesis, natural history, and management. Identified genetic variants in FLG, DSG1, CAPN14, SPINK5, and SPINK7 link EoE to epithelial barrier dysfunction, whereas variants in CCL26, POSTN, and TSLP associate EoE with T helper type 2-mediated immunity. Early-life, infectious, and geographic factors have been implicated in promoting esophageal microbial dysbiosis and, subsequently, T helper type 2 immune responses. However, research into environmental factors and their interaction...
Source: Current Opinion in Immunology - May 24, 2019 Category: Allergy & Immunology Authors: Lyles J, Rothenberg M Tags: Curr Opin Immunol Source Type: research