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Cells Jun 2022The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue,...
The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG. Conversely, IL5 priming did not result in significant eosinophil cytolysis in the same condition. Therefore, to identify critical events protecting eosinophils from cell cytolysis, we examined the differential intracellular events between IL5- and IL3-primed eosinophils interacting with IgG. We showed that both IL3 and IL5 priming increased the eosinophil adhesion to IgG, phosphorylation of p38, and production of reactive oxygen species (ROS), and decreased the phosphorylation of cofilin. However, autophagic flux as measured by the quantification of SQSTM1-p62 and lipidated-MAP1L3CB over time on IgG, with or without bafilomycin-A1, was higher in IL5-primed compared to IL3-primed eosinophils. In addition, treatment with bafilomycin-A1, an inhibitor of granule acidification and autophagolysosome formation, enhanced eosinophil cytolysis and DNA trap formation in IL5-primed eosinophils. Therefore, this study suggests that increased autophagy in eosinophils protects from cytolysis and the release of DNA, and thus limits the discharge of damaging intracellular eosinophilic contents.
Topics: Autophagy; DNA; Eosinophils; Immunoglobulin G; Interleukin-5
PubMed: 35681515
DOI: 10.3390/cells11111821 -
Zeitschrift Fur Rheumatologie May 2019Eosinophilic granulocytes are a subpopulation of leucocytes and part of the innate immune cell pool. Additionally, they have homeostatic functions in different tissues.... (Review)
Review
Eosinophilic granulocytes are a subpopulation of leucocytes and part of the innate immune cell pool. Additionally, they have homeostatic functions in different tissues. Classically, an increased number of eosinophils is associated with allergies and parasitic infections; however, eosinophilia can also be found in vasculitides and malignant tumors. The most important controlling factors of eosinophils are the cytokine interleukin 5 and eotaxins. Eosinophils are able to produce a broad range of signalling factors and toxic proteins, which are stored in cytoplasmic granules and can be quickly and specifically released when needed depending on the stimulus. To combat pathogens, eosinophils can catapult extracellular traps consisting of mitochondrial DNA and toxic proteins into the intercellular space. This review focuses on the basic structure, control and function of eosinophils in health and disease.
Topics: Cytokines; Eosinophilia; Eosinophils; Humans; Inflammation
PubMed: 30627844
DOI: 10.1007/s00393-018-0574-7 -
Trends in Endocrinology and Metabolism:... Jan 2023Gender differences in the functionality of the immune system have been attributed, in part, to direct and indirect effects of sex steroids, especially estrogens, on... (Review)
Review
Gender differences in the functionality of the immune system have been attributed, in part, to direct and indirect effects of sex steroids, especially estrogens, on immune cell repertoire and activity. Notable are studies that have defined roles for estrogens in the regulation of the biology of dendritic cells (DCs), macrophages, T cells and natural killer (NK) cells. Although estrogens can modulate eosinophil function, the mechanisms by which this occurs and how it contributes to the pathobiology of different diseases remains underexplored. Furthermore, although the importance of eosinophils in infection is well established, it remains unclear as to how these innate immune cells, which are present in different tumors, impact the biology of cancer cells and/or response to therapeutics. The observation that eosinophilia influences the efficacy of immune checkpoint blockers (ICBs) is significant considering the role of estrogens as regulators of eosinophil function and recent studies suggesting that response to ICBs is impacted by gender. Thus, in this review, we consider what is known about the roles of estrogen(s) in regulating tissue eosinophilia/eosinophil function and how this influences the pathobiology of breast cancer (in particular). This information provides the context for a discussion of how estrogens/the estrogen receptor (ER) signaling axis can be targeted in eosinophils and how this would be expected to influence the activity of standard-of-care interventions and contemporary immunotherapy regimens in cancer(s).
Topics: Humans; Female; Estrogens; Eosinophilia; Breast Neoplasms; Gonadal Steroid Hormones; Eosinophils
PubMed: 36443206
DOI: 10.1016/j.tem.2022.11.002 -
Annual Review of Pharmacology and... 2015Eosinophil-associated diseases often present with life-threatening manifestations and/or chronic organ damage. Currently available therapeutic options are limited to a... (Review)
Review
Eosinophil-associated diseases often present with life-threatening manifestations and/or chronic organ damage. Currently available therapeutic options are limited to a few drugs that often have to be prescribed on a lifelong basis to keep eosinophil counts under control. In the past 10 years, treatment options and outcomes in patients with clonal eosinophilic and other eosinophilic disorders have improved substantially. Several new targeted therapies have emerged, addressing different aspects of eosinophil expansion and inflammation. In this review, we discuss available and currently tested agents as well as new strategies and drug targets relevant to both primary and secondary eosinophilic diseases, including allergic disorders.
Topics: Animals; Anti-Allergic Agents; Drug Discovery; Eosinophilia; Eosinophils; Humans; Hypersensitivity; Molecular Targeted Therapy; Signal Transduction
PubMed: 25340931
DOI: 10.1146/annurev-pharmtox-010814-124407 -
Journal of Leukocyte Biology Jul 2018Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in... (Review)
Review
Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial-mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal-derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situ hematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non-immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial-mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non-immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease.
Topics: Animals; Cellular Microenvironment; Cytokines; Eosinophils; Hematopoiesis; Homeostasis; Humans
PubMed: 29656559
DOI: 10.1002/JLB.1MR1117-442RR -
Current Allergy and Asthma Reports Jun 2019Eosinophils are short-lived granulocytes that contain a variety of proteins and lipids traditionally associated with host defense against parasites. The primary goal of... (Review)
Review
PURPOSE OF REVIEW
Eosinophils are short-lived granulocytes that contain a variety of proteins and lipids traditionally associated with host defense against parasites. The primary goal of this review is to examine more recent evidence that challenged this rather outdated role of eosinophils in the context of pulmonary infections with helminths, viruses, and bacteria.
RECENT FINDINGS
While eosinophil mechanisms that counter parasites, viruses, and bacteria are similar, the kinetics and impact may differ by pathogen type. Major antiparasitic responses include direct killing and immunoregulation, as well as some mechanisms by which parasite survival/growth is supported. Antiviral defenses may be as unembellished as granule protein-induced direct killing or more urbane as serving as a conduit for better adaptive immune responses to the invading virus. Although sacrificial, eosinophil DNA emitted in response to bacteria helps trap bacteria to limit dissemination. Herein, we discuss the current research redefining eosinophils as multifunctional cells that are active participants in host defense against lung pathogens. Eosinophils recognize and differentially respond to invading pathogens, allowing them to deploy innate defense mechanisms to contain and clear the infection, or modulate the immune response. Modern technology and animal models have unraveled hitherto unknown capabilities of this surreptitious cell that indubitably has more functions awaiting discovery.
Topics: Eosinophils; Humans; Respiratory Tract Infections
PubMed: 31218528
DOI: 10.1007/s11882-019-0867-1 -
Cells May 2023Asthma is a chronic complex pulmonary disease characterized by airway inflammation, remodeling, and hyperresponsiveness. Vascular endothelial growth factor (VEGF) and... (Review)
Review
Asthma is a chronic complex pulmonary disease characterized by airway inflammation, remodeling, and hyperresponsiveness. Vascular endothelial growth factor (VEGF) and eosinophil-derived neurotoxin (EDN) are two significant mediators involved in the pathophysiology of asthma. In asthma, VEGF and EDN levels are elevated and correlate with disease severity and airway hyperresponsiveness. Diversity in VEGF polymorphisms results in the variability of responses to glucocorticosteroids and leukotriene antagonist treatment. Targeting VEGF and eosinophils is a promising therapeutic approach for asthma. We identified lichochalcone A, bevacizumab, azithromycin (AZT), vitamin D, diosmetin, epigallocatechin gallate, IGFBP-3, Neovastat (AE-941), endostatin, PEDF, and melatonin as putative add-on drugs in asthma with anti-VEGF properties. Further studies and clinical trials are needed to evaluate the efficacy of those drugs. AZT reduces the exacerbation rate and may be considered in adults with persistent symptomatic asthma. However, the long-term effects of AZT on community microbial resistance require further investigation. Vitamin D supplementation may enhance corticosteroid responsiveness. Herein, anti-eosinophil drugs are reviewed. Among them are, e.g., anti-IL-5 (mepolizumab, reslizumab, and benralizumab), anti-IL-13 (lebrikizumab and tralokinumab), anti-IL-4 and anti-IL-13 (dupilumab), and anti-IgE (omalizumab) drugs. EDN over peripheral blood eosinophil count is recommended to monitor the asthma control status and to assess the efficacy of anti-IL-5 therapy in asthma.
Topics: Humans; Asthma; Eosinophil-Derived Neurotoxin; Eosinophils; Leukocyte Count; Vascular Endothelial Growth Factor A
PubMed: 37174726
DOI: 10.3390/cells12091326 -
Allergology International : Official... Jan 2021Neutrophils and eosinophils are granulocytes which are characterized by the presence of granules in the cytoplasm. Granules provide a safe storage site for granule... (Review)
Review
Neutrophils and eosinophils are granulocytes which are characterized by the presence of granules in the cytoplasm. Granules provide a safe storage site for granule proteins that play important roles in the immune function of granulocytes. Upon granulocytes activation, diverse proteins are released from the granules into the extracellular space and contribute to the fight against infections. In this article, we describe granule proteins of both neutrophils and eosinophils able to kill pathogens and review their anticipated mechanism of antimicrobial toxicity. It should be noted that an excess of granules protein release can lead to tissue damage of the host resulting in chronic inflammation and organ dysfunction.
Topics: Cell Communication; Cytotoxicity, Immunologic; Disease Susceptibility; Eosinophil Granule Proteins; Eosinophils; Extracellular Space; Host-Pathogen Interactions; Humans; Immunity, Innate; Neutrophils
PubMed: 33277190
DOI: 10.1016/j.alit.2020.11.003 -
Mucosal Immunology Nov 2021Expression of Ikaros family transcription factor IKZF3 (Aiolos) increases during murine eosinophil lineage commitment and maturation. Herein, we investigated Aiolos...
Expression of Ikaros family transcription factor IKZF3 (Aiolos) increases during murine eosinophil lineage commitment and maturation. Herein, we investigated Aiolos expression and function in mature human and murine eosinophils. Murine eosinophils deficient in Aiolos demonstrated gene expression changes in pathways associated with granulocyte-mediated immunity, chemotaxis, degranulation, ERK/MAPK signaling, and extracellular matrix organization; these genes had ATAC peaks within 1 kB of the TSS that were enriched for Aiolos-binding motifs. Global Aiolos deficiency reduced eosinophil frequency within peripheral tissues during homeostasis; a chimeric mouse model demonstrated dependence on intrinsic Aiolos expression by eosinophils. Aiolos deficiency reduced eosinophil CCR3 surface expression, intracellular ERK1/2 signaling, and CCL11-induced actin polymerization, emphasizing an impaired functional response. Aiolos-deficient eosinophils had reduced tissue accumulation in chemokine-, antigen-, and IL-13-driven inflammatory experimental models, all of which at least partially depend on CCR3 signaling. Human Aiolos expression was associated with active chromatin marks enriched for IKZF3, PU.1, and GATA-1-binding motifs within eosinophil-specific histone ChIP-seq peaks. Furthermore, treating the EOL-1 human eosinophilic cell line with lenalidomide yielded a dose-dependent decrease in Aiolos. These collective data indicate that eosinophil homing during homeostatic and inflammatory allergic states is Aiolos-dependent, identifying Aiolos as a potential therapeutic target for eosinophilic disease.
Topics: Allergens; Animals; Chemotaxis, Leukocyte; Disease Susceptibility; Eosinophils; Female; Gene Expression Profiling; Gene Expression Regulation; Granulocytes; Humans; Ikaros Transcription Factor; Immunity, Innate; Immunophenotyping; Leukocyte Count; Male; Mice; Mice, Knockout; Models, Animal; Receptors, CCR3; Signal Transduction
PubMed: 34341502
DOI: 10.1038/s41385-021-00416-4 -
Memorias Do Instituto Oswaldo Cruz 1997While the eosinophil's effector functions clearly can contribute to the pathogenesis of allergic diseases, the evolutionary benefit to having eosinophils as a distinct... (Review)
Review
While the eosinophil's effector functions clearly can contribute to the pathogenesis of allergic diseases, the evolutionary benefit to having eosinophils as a distinct class of leukocyte is not clear, especially if one must reconsider the nominally beneficial role of eosinophils in parasite host defense, Eosinophils are equipped to respond to lymphocytes and their cytokines (and not solely the eosinophil growth factor cytokines), but the functional consequences of such eosinophil responses need to be defined. Conversely, eosinophils, as antigen-presenting cells (APCs) or sources of lymphocyte-active cytokines, may stimulate and affect lymphocyte functioning. Eosinophils share with CD4+ lymphocytes expression of a number of receptors, including CD4 and IL-2R, and specific alpha-4 integrins that may help in their common recruitment and activation. Further, elucidation of the interactions between lymphocytes and eosinophils will contribute to a broader understanding of the functioning of eosinophils in "normal" ongoing immune responses and in allergic disorders.
Topics: Cell Communication; Cytokines; Eosinophils; Humans; Hypersensitivity; Lymphocytes
PubMed: 9698930
DOI: 10.1590/s0074-02761997000800023