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Frontiers in Immunology 2014Neutrophils are part of a family of granulocytes that, together with eosinophils and basophils, play an essential role in innate immunity. Neutrophils are the most... (Review)
Review
Neutrophils are part of a family of granulocytes that, together with eosinophils and basophils, play an essential role in innate immunity. Neutrophils are the most abundant circulating leukocytes and are vital for rapid immune responses, being recruited to sites of injury or infection within minutes, where they can act as specialized phagocytic cells. However, another prominent function of neutrophils is the release of pro-inflammatory compounds, including cytokines, chemokines, and digestive enzymes, which are stored in intracellular compartments and released through regulated exocytosis. Hence, an important feature that contributes to rapid immune responses is capacity of neutrophils to synthesize and store pre-formed pro-inflammatory mediators in specialized intracellular vesicles and thus no new synthesis is required. This review will focus on advancement in three topics relevant to neutrophil secretion. First, we will examine what is known about basal level pro-inflammatory mediator synthesis, trafficking, and storage in secretory compartments. Second, we will review recent advancements in the mechanisms that control vesicle mobilization and the release of pre-formed mediators. Third, we will examine the upregulation and de novo synthesis of pro-inflammatory mediators by neutrophils engaged at sites of infection.
PubMed: 25285096
DOI: 10.3389/fimmu.2014.00448 -
European Journal of Immunology Aug 2012Over the past decade, a growing recognition of the importance of neutralizing antibodies in host defense combined with the success of B-cell depletion therapies in... (Review)
Review
Over the past decade, a growing recognition of the importance of neutralizing antibodies in host defense combined with the success of B-cell depletion therapies in treating auto-immune disorders has led to an increased focus on better understanding the pathways underpinning B-cell antibody production. In general, B cells require cognate interaction with T helper cells in the germinal center of lymphoid follicles to generate protective antibodies. However, recent evidence shows that B cells receive additional help from invariant natural killer T cells, dendritic cells, and various granulocytes, including neutrophils, eosinophils, and basophils. These innate immune cells enhance T-cell-dependent antibody responses by delivering B-cell helper signals both in the germinal center and at postgerminal center lymphoid sites such as the bone marrow. In addition to enhancing and complementing the B-cell helper activity of canonical T cells, invariant natural killer T cells, dendritic cells, and granulocytes can deliver T cell-independent B-cell helper signals at the mucosal interface and in the marginal zone of the spleen to initiate rapid innate-like antibody responses. Here, we discuss recent advances in the role of adaptive and innate B-cell helper signals in antibody diversification and production.
Topics: Adaptive Immunity; Antibody Formation; B-Lymphocytes; Bone Marrow; Cell Communication; Dendritic Cells; Germinal Center; Granulocytes; Humans; Immunity, Innate; Lymphocyte Activation; Lymphoid Tissue; Natural Killer T-Cells; Signal Transduction; Spleen; T-Lymphocytes, Helper-Inducer
PubMed: 22865046
DOI: 10.1002/eji.201242594 -
Cells Jun 2021venom allergy is one of the most severe allergic diseases, with a considerable prevalence of anaphylactic reaction, making it potentially lethal. In this review, we... (Review)
Review
venom allergy is one of the most severe allergic diseases, with a considerable prevalence of anaphylactic reaction, making it potentially lethal. In this review, we provide an overview of the current knowledge and recent findings in understanding induced immune mechanisms during different phases of venom immunotherapy. We focus on protection mechanisms that occur early, during the build-up phase, and on the immune tolerance, which occurs later, during and after venom immunotherapy. The short-term protection seems to be established by the early desensitization of mast cells and basophils, which plays a crucial role in preventing anaphylaxis during the build-up phase of treatment. The early generation of blocking IgG antibodies seems to be one of the main reasons for the lower activation of effector cells. Long-term tolerance is reached after at least three years of venom immunotherapy. A decrease in basophil responsiveness correlates with tolerated sting challenge. Furthermore, the persistent decline in IgE levels and, by monitoring the cytokine profiles, a shift from a Th2 to Th1 immune response, can be observed. In addition, the generation of regulatory T and B cells has proven to be essential for inducing allergen tolerance. Most studies on the mechanisms and effectiveness data have been obtained during venom immunotherapy (VIT). Despite the high success rate of VIT, allergen tolerance may not persist for a prolonged time. There is not much known about immune mechanisms that assure long-term tolerance post-therapy.
Topics: Animals; Arthropod Venoms; Desensitization, Immunologic; Humans; Immune Tolerance; Models, Biological; Models, Immunological; Time Factors
PubMed: 34206562
DOI: 10.3390/cells10071575 -
Human Vaccines & Immunotherapeutics Oct 2012IgE-mediated allergy is a highly prevalent disease in the industrialized world. Allergen-specific immunotherapy (SIT) should be the preferred treatment, as it has long... (Review)
Review
IgE-mediated allergy is a highly prevalent disease in the industrialized world. Allergen-specific immunotherapy (SIT) should be the preferred treatment, as it has long lasting protective effects and can stop the progression of the disease. However, few allergic patients choose to undergo SIT, due to the long treatment time and potential allergic adverse events. Since the beneficial effects of SIT are mediated by antigen presenting cells inducing Th1, Treg and antibody responses, whereas the adverse events are caused by mast cells and basophils, the therapeutic window of SIT may be widened by targeting tissues rich in antigen presenting cells. Lymph nodes and the epidermis contain high density of dendritic cells and low numbers of mast cells and basophils. The epidermis has the added benefit of not being vascularised thereby reducing the chances of anaphylactic shock due to leakage of allergen. Hence, both these tissues represent highly promising routes for SIT and are the focus of discussion in this review.
Topics: Animals; Desensitization, Immunologic; Drug Administration Routes; Humans
PubMed: 23095873
DOI: 10.4161/hv.21948 -
Frontiers in Immunology 2020Basophil activation tests (BATs) can closely monitor, , a patient's propensity to develop type I hypersensitivity reactions. Because of their high specificity and... (Review)
Review
Basophil activation tests (BATs) can closely monitor, , a patient's propensity to develop type I hypersensitivity reactions. Because of their high specificity and sensitivity, BATs have become promising diagnostic tools, especially in cases with equivocal clinical histories, skin prick test results, and/or levels of specific IgE to allergen extracts. BATs also are useful as tools for monitoring the effects of treatment, since oral immunotherapy (OIT) studies report a diminution in patients' basophil responsiveness over the course of OIT. This review will discuss the BAT findings obtained before, during, and after OIT for food allergy. We will mainly focus on the association of basophil responsiveness, and alterations in basophil surface markers, with clinical outcomes and other clinical features, such as blood levels of specific IgG and IgE antibodies. The detailed analysis of these correlations will ultimately facilitate the use of BATs, along with other blood biomarkers, to differentiate short-term desensitization versus sustained unresponsiveness and to improve treatment protocols. Given the critical anatomic location of mast cells adjacent to the many IgE plasma cells found in the gastrointestinal tissues of allergic individuals, we will also discuss the role of gastrointestinal mast cells in manifestations of food allergies.
Topics: Administration, Oral; Allergens; Basophil Degranulation Test; Basophils; Biomarkers; Cell Degranulation; Desensitization, Immunologic; Food Hypersensitivity; Humans; Immunoglobulin E; Immunoglobulin G; Mast Cells; Predictive Value of Tests; Skin Tests; Treatment Outcome
PubMed: 33381123
DOI: 10.3389/fimmu.2020.602660 -
Frontiers in Immunology 2015Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high-affinity... (Review)
Review
Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high-affinity receptor for IgE (FcεR1), release histamine, inflammatory mediators, and cytokines following FcεR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid, and non-lymphoid tissues, and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcεR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naïve T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2, and Th17 cells, as well as their potential role in IgE-independent non-allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases.
PubMed: 26284078
DOI: 10.3389/fimmu.2015.00399 -
Infection and Immunity May 2015Interleukin-33 (IL-33) has now emerged as a cytokine with diverse and pleiotropic functions in various infectious and inflammatory diseases. IL-33 is expressed by... (Review)
Review
Interleukin-33 (IL-33) has now emerged as a cytokine with diverse and pleiotropic functions in various infectious and inflammatory diseases. IL-33 is expressed by epithelial cells, endothelial cells, fibroblasts, and hepatocytes. The target cells of IL-33 are Th2 cells, basophils, dendritic cells, mast cells, macrophages, NKT cells, and nuocytes, newly discovered natural helper cells/innate lymphoid cells bearing the ST2 receptor. IL-33 has dual functions, both as a traditional cytokine and as a nuclear factor that regulates gene transcription. IL-33 functions as an "alarmin" released following cell death, as a biomarker, and as a vaccine adjuvant, with proinflammatory and protective effects during various infections. The exacerbated or protective role of the IL-33/ST2 axis during different infections is dependent upon the organ involved, type of infectious agent, whether the infection is acute or chronic, the invasiveness of the infectious agent, the host immune compartment, and cellular and cytokine microenvironments. In this review, we focus on recent advances in the understanding of the role of the IL-33/ST2 axis in various viral, bacterial, fungal, helminth, and protozoal infectious diseases gained from animal models and studies in human patients. The functional role of IL-33 and ST2 during experimentally induced infections has been summarized by accumulating the data for IL-33- and ST2-deficient mice or for mice exogenously administered IL-33. In summary, exploring the crucial and diverse roles of the IL-33/ST2 axis during infections may help in the development of therapeutic interventions for a wide range of infectious diseases.
Topics: Animals; Communicable Diseases; Disease Models, Animal; Humans; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins; Mice, Knockout; Receptors, Cell Surface; Receptors, Interleukin
PubMed: 25712928
DOI: 10.1128/IAI.02908-14 -
The World Allergy Organization Journal Feb 2020Respiratory allergies are important medical conditions because they affect nearly 20% of the population worldwide, with higher prevalence in industrialized cities....
Respiratory allergies are important medical conditions because they affect nearly 20% of the population worldwide, with higher prevalence in industrialized cities. Aeroallergens such as pollen are responsible for up to 40% of respiratory allergies. The pollen from (privet hedge) is a great source of inhalant allergens associated with allergic respiratory diseases around the world. However, it has been underestimated as a sensitization factor. Interestingly, over the last few years a number of novel allergens have been identified from using immunoproteomics technologies. Cross-linking of IgE and allergens could lead to the rapid release of inflammatory mediators by mast cells and basophils. These will promote a late response characterized by activation of T cells and overproduction of Th2 cytokines such as IL-4, IL-5, IL-9, and IL-13. These inflammatory changes cause respiratory diseases like asthma and allergic rhinitis in sensitized subjects. Here, we review pollen allergens and focus on their clinical and immunological significance in allergic disease as well as the use of hypoallergenic derivatives in personalized therapy.
PubMed: 32055279
DOI: 10.1016/j.waojou.2020.100104 -
Frontiers in Immunology 2018The survival of helminths in the host over long periods of time is the result of a process of adaptation or dynamic co-evolution between the host and the parasite.... (Review)
Review
The survival of helminths in the host over long periods of time is the result of a process of adaptation or dynamic co-evolution between the host and the parasite. However, infection with helminth parasites causes damage to the host tissues producing the release of danger signals that induce the recruitment of various cells, including innate immune cells such as macrophages (Mo), dendritic cells (DCs), eosinophils, basophils, and mast cells. In this scenario, these cells are able to secrete soluble factors, which orchestrate immune effector mechanisms that depend on the different niches these parasites inhabit. Here, we focus on recent advances in the knowledge of excretory-secretory products (ESP), resulting from helminth recognition by DCs and Mo. Phagocytes and other cells types such as innate lymphocyte T cells 2 (ILC2), when activated by ESP, participate in an intricate cytokine network to generate innate and adaptive Th2 responses. In this review, we also discuss the mechanisms of innate immune cell-induced parasite killing and the tissue repair necessary to assure helminth survival over long periods of time.
Topics: Animals; Dendritic Cells; Helminthiasis; Helminths; Host-Parasite Interactions; Humans; Immunity, Innate; Immunomodulation; Macrophages; Pathogen-Associated Molecular Pattern Molecules; Phagocytes; Th2 Cells
PubMed: 29670630
DOI: 10.3389/fimmu.2018.00664 -
Frontiers in Immunology 2020Despite attempts to halt it, the prevalence of food allergy is increasing, and there is an unmet need for strategies to prevent morbidity and mortality from food-induced... (Review)
Review
Despite attempts to halt it, the prevalence of food allergy is increasing, and there is an unmet need for strategies to prevent morbidity and mortality from food-induced allergic reactions. There are no known medications that can prevent anaphylaxis, but several novel therapies show promise for the prevention of food-induced anaphylaxis through targeting of the high-affinity IgE receptor (FcϵRI) pathway. This pathway includes multiple candidate targets, including tyrosine kinases and the receptor itself. Small molecule inhibitors of essential kinases have rapid onset of action and transient efficacy, which may be beneficial for short-term use for immunotherapy buildup or desensitizations. Short courses of FDA-approved inhibitors of Bruton's tyrosine kinase can eliminate IgE-mediated basophil activation and reduce food skin test size in allergic adults, and prevent IgE-mediated anaphylaxis in humanized mice. In contrast, biologics may provide longer-lasting protection, albeit with slower onset. Omalizumab is an anti-IgE antibody that sequesters IgE, thereby reducing FcϵRI expression on mast cells and basophils. As a monotherapy, it can increase the clinical threshold dose of food allergen, and when used as an adjunct for food immunotherapy, it decreases severe reactions during buildup phase. Finally, lirentelimab, an anti-Siglec-8 antibody currently in clinical trials, can prevent IgE-mediated anaphylaxis in mice through mast cell inhibition. This review discusses these and other emerging therapies as potential strategies for preventing food-induced anaphylaxis. In contrast to other food allergy treatments which largely focus on individual allergens, blockade of the FcϵRI pathway has the advantage of preventing clinical reactivity from any food.
Topics: Agammaglobulinaemia Tyrosine Kinase; Anaphylaxis; Animals; Anti-Allergic Agents; Basophils; Food Hypersensitivity; Humans; Immunoglobulin E; Mast Cells; Mice; Omalizumab; Protein Tyrosine Phosphatases; Receptors, IgE; Sialic Acid Binding Immunoglobulin-like Lectins; Signal Transduction
PubMed: 33391286
DOI: 10.3389/fimmu.2020.614402