A single dose of angiotensin-(1-7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge.

OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.

Extracellular sombrero vesicles are hallmarks of eosinophilic cytolytic degranulation in tissue sites of human diseases.

Eosinophil sombrero vesicles are large tubular carriers resident in the cytoplasm of human eosinophils, identifiable by transmission electron microscopy, and important for immune mediator transport. Increased formation of sombrero vesicles occurs in activated eosinophils in vitro and in vivo. In tissue sites of eosinophilic cytolytic inflammation, extracellular eosinophil sombrero vesicles are noted, but their frequency and significance in eosinophil-associated diseases remain unclear. Here, we performed comprehensive quantitative transmission electron microscopy analyses and electron tomography to investigate the numbers, density, integrity, and 3-dimensional structure of eosinophil sombrero vesicles in different biopsy tissues from 5 prototypic eosinophil-associated diseases (eosinophilic chronic rhinosinusitis/nasal sinuses, ulcerative colitis/intestines, hypereosinophilic syndrome/skin, dermatitis/skin, and schistosomiasis/rectum). The morphology of extracellular eosinophil sombrero vesicles was also compared with that of cytoplasmic eosinophil sombrero vesicles, isolated by subcellular fractionation from peripheral blood eosinophils. We demonstrated that (i) eosinophil cytolysis, releasing intact sombrero vesicles and membrane-bound granules, is a consistent event in all eosinophil-associated diseases; (ii) eosinophil sombrero vesicles persist intact even after complete disintegration of all cell organelles, except granules (late cytolysis); (iii) the eosinophil sombrero vesicle population, composed of elongated, curved, and typical sombreros, and the eosinophil sombrero vesicle 3-dimensional architecture, diameter, and density remain unchanged in the extracellular matrix; (iv) free eosinophil sombrero vesicles closely associate with extracellular granules; and (v) free eosinophil sombrero vesicles also associate with externalized chromatin during eosinophil ETosis. Remarkably, eosinophil sombrero vesicles appeared on the surface of other cells, such as plasma cells. Thus, eosinophil cytolysis/ETosis can secrete intact sombrero vesicles, alongside granules, in inflamed tissues of eosinophil-associated diseases, potentially serving as propagators of eosinophil immune responses after cell death.

Eosinophil activation during immune responses: an ultrastructural view with an emphasis on viral diseases.

Eosinophils are cells of the innate immune system that orchestrate complex inflammatory responses. The study of the cell biology of eosinophils, particularly associated with cell activation, is of great interest to understand their immune responses. From a morphological perspective, activated eosinophils show ultrastructural signatures that have provided critical insights into the comprehension of their functional capabilities. Application of conventional transmission electron microscopy in combination with quantitative assessments (quantitative transmission electron microscopy), molecular imaging (immunoEM), and 3-dimensional electron tomography have generated important insights into mechanisms of eosinophil activation. This review explores a multitude of ultrastructural events taking place in eosinophils activated in vitro and in vivo as key players in allergic and inflammatory diseases, with an emphasis on viral infections. Recent progress in our understanding of biological processes underlying eosinophil activation, including in vivo mitochondrial remodeling, is discussed, and it can bring new thinking to the field.

The absence of eosinophils is associated with early metastatic lesions in Leishmania amazonensis-infected mice

BACKGROUND Eosinophils are granulocytes that rapidly increase frequency in the bloodstream during helminthic infections and allergic responses. They are found in tissue infected by Leishmania during early disease, but their role during infection is not entirely understood. OBJECTIVES We aim to compare the disease due to Leishmania amazonensis in BALB/c and Δdbl-GATA1 mice, which lack eosinophils. METHODS BALB/c and Δdbl-GATA1 mice infected with L. amazonensis were observed for several weeks. The parasite load and dissemination pattern were assessed. FINDINGS The Δdbl-GATA1 mice developed an anticipated dissemination of L. amazonensis and a worsening disease. No differences were found in the lesion development or the parasite load in the footpad among Δdbl-GATA1 mice and BALB/c eight weeks after infection. However, nine weeks after infection, massive growth of metastatic lesions appeared in several parts of the skin in Δdbl-GATA1 mice, weeks earlier than BALB/c. We observed increased parasites in the bloodstream, probably an essential dissemination route. Thirteen weeks after infection, metastatic lesions were found in all Δdbl-GATA1 mice. MAIN CONCLUSION These results suggest a protective role of eosinophils in delaying the disease caused by L. amazonensis, although several limitations of this mice strain must be considered.

Economic evidence supports the cost savings of sputum eosinophil counts to guide the treatment of pediatrics patients with persistent asthma: implications for clinical practice guidelines in middle-income countries.

BACKGROUND: Tailoring asthma interventions based on biomarkers could substantially impact the high cost associated with asthma morbidity. For policymakers, the main concern is the economic impact of adopting this technology, especially in developing countries. This study evaluates the budget impact of asthma management using sputum eosinophil counts in Colombia patients between 4 and 18 years of age. METHODS: A budget impact analysis was performed to evaluate the potential financial impact of sputum eosinophil counts (EO). The study considered a 5-year time horizon and the Colombian National Health System perspective. The incremental budget impact was calculated by subtracting the cost of the new treatment, in which EO is reimbursed, from the cost of the conventional therapy without EO (management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma-related). Univariate one-way sensitivity analyses were performed. RESULTS: In the base-case analysis, the 5-year costs associated with EO and no-EO were estimated to be US$ 532.865.915 and US$ 540.765.560, respectively, indicating savings for Colombian National Health equal to US$ 7.899.645, if EO is adopted for the routine management of patients with persistent asthma. This result was robust in univariate sensitivity one-way analysis. CONCLUSION: EO was cost-saving in guiding the treatment of patients between 4 and 18 years of age with persistent asthma. Decision-makers in our country can use this evidence to improve clinical practice guidelines, and it should be replicated to validate their results in other middle-income countries.

IL-22 Is Deleterious along with IL-17 in Allergic Asthma but Is Not Detrimental in the Comorbidity Asthma and Acute Pneumonia.

There is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. To investigate the role of IL-22, we used IL-22 deficient mice (IL-22 KO) sensitized and challenged with ovalbumin (OVA) and compared with wild type (WT) animals exposed to OVA. IL-22 KO animals exposed to OVA showed a decreased number and frequency of eosinophils, IL-5 and IL-13 in the airways, reduced mucus production and pulmonary inflammation. In addition, IL-22 KO animals exhibited a decreased percentage and number of lung CD11c+CD11b+ cells and increased apoptosis of eosinophils. Th17 cell transfer generated from IL-22 KO to animals previously sensitized and challenged with OVA caused a reduction in eosinophil frequency and number in the airways compared to animals transferred with Th17 cells generated from WT mice. Therefore, IL-22 is deleterious with concomitant secretion of IL-17. Our findings show a pro-inflammatory role for IL-22, confirmed in a model of allergen-free and allergen-specific immunotherapy. Moreover, during the comorbidity asthma and pneumonia that induces neutrophil inflammation, IL-22 was not detrimental. Our results show that targeting IL-22 would negatively affect the survival of eosinophils, reduce the expansion or migration of CD11c+CD11b+ cells, and negatively regulate allergic asthma.

Eosinophils: Focus on DNA extracellular traps.

Eosinophils are multitasking granulocytes with implications for allergies, host response to helminths and, more recently, described roles in immunomodulation, homeostasis and tissue remodeling. Eosinophils secrete their preformed granule proteins by different pathways, especially piecemeal degranulation and cytolysis with granule release. Currently, there are different insights related to eosinophils' functional roles and biology that deserve to be highlighted. Cytolysis with granule release has also been associated with DNA extracellular trap formation, one of the most intriguing, recently described mechanisms of leukocyte activation. Focusing on DNA extracellular trap release, there are lessons to be learned from neutrophils considering the multitasking roles of these structures in inflammation, and the mechanisms involved in their release. This review explores a comparative analysis of the current knowledge considering DNA traps extrusion in neutrophils and eosinophils and update the major findings regarding the presence of these entities in eosinophilic-associated immune responses, inflammation and diseases.

Schistosomiasis Mansoni-Recruited Eosinophils: An Overview in the Granuloma Context.

Eosinophils are remarkably recruited during schistosomiasis mansoni, one of the most common parasitic diseases worldwide. These cells actively migrate and accumulate at sites of granulomatous inflammation termed granulomas, the main pathological feature of this disease. Eosinophils colonize granulomas as a robust cell population and establish complex interactions with other immune cells and with the granuloma microenvironment. Eosinophils are the most abundant cells in granulomas induced by Schistosoma mansoni infection, but their functions during this disease remain unclear and even controversial. Here, we explore the current information on eosinophils as components of Schistosoma mansoni granulomas in both humans and natural and experimental models and their potential significance as central cells triggered by this infection.

Autoimmune hepatitis presenting with peripheral eosinophilia: Case report and literature review.

Acute hepatitis presenting with blood eosinophilia are scarcely reported. Different clinical courses of autoimmune hepatitis (AIH) have been associated with acute hepatitis with eosinophilia, however it is still unclear if the latter is a common manifestation of different autoimmune diseases, part of a similar spectrum of eosinophil-associated liver injury or even a trigger to AIH. We report a case of a 32 years old woman who presented with subacute hepatitis, peripheral eosinophilia, hypergammaglobulinemia and liver biopsy suggestive of AIH. The role of eosinophils in autoimmune liver diseases deserves further studies in order to clarify its physiopathology aspects.

In Vivo ETosis of Human Eosinophils: The Ultrastructural Signature Captured by TEM in Eosinophilic Diseases.

Eosinophilic diseases, also termed eosinophil-associated diseases (EADs), are characterized by eosinophil-rich inflammatory infiltrates and extensive eosinophil degranulation with clinically relevant organ pathology. Recent evidence shows that eosinophil cytolytic degranulation, that is, the release of intact, membrane-delimited granules that arises from the eosinophil cytolysis, occurs mainly through ETosis, meaning death with a cytolytic profile and extrusion of nucleus-originated DNA extracellular traps (ETs). The ultrastructural features of eosinophil ETosis (EETosis) have been studied mostly in vitro after stimulation, but are still poorly understood in vivo. Here, we investigated in detail, by transmission electron microscopy (TEM), the ultrastructure of EETosis in selected human EADs affecting several tissues and organ systems. Biopsies of patients diagnosed with eosinophilic chronic rhinosinusitis/ECRS (frontal sinus), ulcerative colitis/UC (intestine), and hypereosinophilic syndrome/HES (skin) were processed for conventional TEM. First, we found that a large proportion of tissue-infiltrated eosinophils in all diseases (~45-65% of all eosinophils) were undergoing cytolysis with release of free extracellular granules (FEGs). Second, we compared the morphology of tissue inflammatory eosinophils with that shown by in vitro ETosis-stimulated eosinophils. By applying single-cell imaging analysis, we sought typical early and late EETosis events: chromatin decondensation; nuclear delobulation and rounding; expanded nuclear area; nuclear envelope alterations and disruption; and extracellular decondensed chromatin spread as ETs. We detected that 53% (ECRS), 37% (UC), and 82% (HES) of all tissue cytolytic eosinophils had ultrastructural features of ETosis in different degrees. Eosinophils in early ETosis significantly increased their nuclear area compared to non-cytolytic eosinophils due to excessive chromatin decondensation and expansion observed before nuclear envelope disruption. ETosis led not only to the deposition of intact granules, but also to the release of eosinophil sombrero vesicles (EoSVs) and Charcot-Leyden crystals (CLCs). Free intact EoSVs and CLCs were associated with FEGs and extracellular DNA nets. Interestingly, not all cytolytic eosinophils in the same microenvironment exhibited ultrastructure of ETosis, thus indicating that different populations of eosinophils might be selectively activated into this pathway. Altogether, our findings captured an ultrastructural signature of EETosis in vivo in prototypic EADs highlighting the importance of this event as a form of eosinophil degranulation and release of inflammatory markers (EoSVs and CLCs).

Influence of Consumption of Two Peruvian Cocoa Populations on Mucosal and Systemic Immune Response in an Allergic Asthma Rat Model.

Different cocoa populations have demonstrated a protective role in a rat model of allergic asthma by attenuating the immunoglobulin (Ig) E synthesis and partially protecting against anaphylactic response. The aim of this study was to ascertain the effect of diets containing two native Peruvian cocoa populations ("Amazonas Peru" or APC, and "Criollo de Montaña" or CMC) and an ordinary cocoa (OC) on the bronchial compartment and the systemic and mucosal immune system in the same rat model of allergic asthma. Among other variables, cells and IgA content in the bronchoalveolar lavage fluid (BALF) and serum anti-allergen antibody response were analyzed. The three cocoa populations prevented the increase of the serum specific IgG1 (T helper 2 isotype). The three cocoa diets decreased asthma-induced granulocyte increase in the BALF, which was mainly due to the reduction in the proportion of eosinophils. Moreover, both the OC and CMC diets were able to prevent the leukocyte infiltration caused by asthma induction in both the trachea and nasal cavity and decreased the IgA in both fecal and BALF samples. Overall, these results highlight the potential of different cocoa populations in the prevention of allergic asthma.

Kinetics of Eosinophils during Development of the Cellular Infiltrate Surrounding the Nurse Cell of Trichinella spiralis in Experimentally Infected Mice.

We study the kinetics of eosinophils during the development of the cellular infiltrate surrounding the nurse cell of Trichinella spiralis (T. spiralis) in experimentally infected mice. Male CD1 mice were experimentally infected with 50 viable muscle larvae of the MSUS/MEX/91/CM-91 T. spiralis strain. Tongues and diaphragms were obtained daily from days 13 to 39 post infection. Diaphragms were compressed and subjected to Giemsa stain. Tongues were histologically sectioned and stained with erythrosine B or hematoxylin and eosin. The cellular infiltrate and the nurse cell-larva complex were detected by optical microscopy since day 16 post infection. The size of the larva increased exponentially during the course of the infection. The kinetics of eosinophils showed a multimodal trend, with a bimodal predominance. The maximum peaks were reached on days 21 and 27 post infection. The results of this study demonstrate that eosinophils occur abundantly in two transcendent moments of the T. spiralis life cycle: first, when the stage 1 larva invades the myocyte and second when the nurse cell-larva complex has been fully developed. These results help one to understand the immunobiology of T. spiralis, highlighting the importance of eosinophils in the survival of the larva in skeletal muscle. Further studies are needed to characterize the cell populations that comprise the cellular infiltrate during the development of the mother cell.

Cysteinyl leukotriene induces eosinophil extracellular trap formation via cysteinyl leukotriene 1 receptor in a murine model of asthma.

PURPOSE: Eosinophils are one of the main cells responsible to the inflammatory response in asthma by the release of inflammatory molecules such as cytokines, reactive oxygen species (ROS), cytotoxic granule, eosinophil extracellular trap (EET), and lipid mediators as cysteinyl leukotriene (cysLT). The interconnections between these molecules are not fully understood. Here, we attempted to investigate the cysLT participation in the mechanisms of EET formation in an asthma model of OVA challenge. MATERIALS AND METHODS: Before intranasal challenge with OVA, BALB/cJ mice were treated with a 5-lipoxygenase-activating protein (FLAP) inhibitor (MK-886), or with a cysLT1 receptor antagonist (MK-571) and the lung and bronchoalveolar lavage fluid (BALF) were analyzed. RESULTS: We showed that OVA-challenged mice treated with MK-886 or MK-571 had a decrease in inflammatory cells, goblet cells hyperplasia, and eosinophil peroxidase (EPO) activity in the airway. However, only OVA-challenged mice treated with MK-571 had an improvement in lung function. Also, treatments with MK-886 or MK-571 decreased Th2 cytokines levels in the airway. Moreover, we observed that OVA-challenged mice treated with MK-886 or MK-571 had a decrease in EET formation in BALF. We also verified that EET release was not due to cell death because the cell viability remained the same among the groups. CONCLUSION: We revealed that the decrease in cysLT production or cysLT1 receptor inhibition by MK-886 or/and MK-571 treatments, respectively reduced EET formation in BALF, showing that cysLT regulates the activation process of EET release in asthma.

Presence of IgE Autoantibodies Against Eosinophil Peroxidase and Eosinophil Cationic Protein in Severe Chronic Spontaneous Urticaria and Atopic Dermatitis.

PURPOSE: Eosinophils are frequently found in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) that release eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP). Continuous exposure to these proteins could trigger an autoimmune response which may contribute to the pathogenesis and severity of skin inflammation. In this study, we investigate the immunoglobulin E (IgE) response against eosinophil proteins in CSU and AD. METHODS: We recruited patients with severe AD, severe CSU and healthy subjects to explore the presence of IgE autoantibodies and cross-reactivity against EPX, ECP and thyroid peroxidase (TPO). The potential cross-reactive epitopes among the peroxidase family were determined using in silico tools. RESULTS: The frequencies of anti-EPX IgE (28.8%) and anti-ECP IgE (26.6%) were higher in the AD group, and anti-TPO IgE was higher in the CSU group (27.2%). In the CSU group, there was a correlation between the anti-EPX IgE and anti-TPO IgE levels (r = 0.542, P < 0.001); TPO inhibited 42% of IgE binding to EPX, while EPX inhibited 59% of IgE binding to TPO, suggesting a cross-reactivity with EPX as a primary sensitizer. There was greater inhibition when we used a pool of sera CSU and AD, TPO inhibited 52% of IgE binding to EPX, while EPX inhibited 78% of IgE binding to TPO. In silico analysis showed a possible shared epitope in the peroxidase protein family. CONCLUSIONS: IgE against eosinophil proteins may contribute to chronic inflammation in patients with AD and CSU. Cross-reactivity between EPX and TPO could explain thyroid problems in CSU patients.

Human Eosinophils Reduce Viral Titer, Secrete IL-8, and Increase RIG-I Expression in Response to Influenza A H1N1 pdm09.

Eosinophils participate in the immune response against many pathogens, including viruses. Since mouse eosinophils are susceptible to influenza A virus infection and possess antiviral activity, we evaluated the expression of sialic acid residues in human eosinophils and their response against influenza virus in vitro. We demonstrated that human eosinophils express α2,6- and α2,3-linked sialic acid, and drastically reduced influenza virus titer. After influenza virus exposure, eosinophils upregulated retinoic acid-inducible gene I (RIG-I) mRNA expression, but no other pattern recognition receptors. Finally, high concentrations of interleukin-8 (IL-8) were found in influenza virus-exposed eosinophil cultures. These data suggest that human eosinophils possess antiviral activity and may play a role in the innate immune response to influenza virus.

The Immune System Throws Its Traps: Cells and Their Extracellular Traps in Disease and Protection.

The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described-suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others. This review discusses the presence of ETs in neutrophils, macrophages, mast cells, eosinophils, basophils, plasmacytoid dendritic cells, and recent evidence of the presence of ETs in B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes. Moreover, due to recently collected information, the effect of ETs on COVID-19 is also discussed.

Biomarkers as a Prognostic Factor in COPD Exacerbation: A Cohort Study.

The acute exacerbations of COPD (AECOPD) are one of the main causes of hospitalization and morbimortality in the adult population. There are not many tools available to predict the clinical course of these patients during exacerbations. Our goal was to estimate the clinical utility of C Reactive Protein (CRP), Mean Platelet Volume (MPV), eosinophil count and neutrophil/lymphocyte ratio (NLR) as in-hospital prognostic factors in patients with AECOPD. A prospective cohort study was conducted in patients who consulted three reference hospitals in the city of Medellín for AECOPD and who required hospitalization between 2017 and 2020. A multivariate analysis was performed to estimate the effect of biomarkers in the two primary outcomes: the composite outcome of in-hospital death and/or admission to the ICU and hospital length-of-stay. A total of 610 patients with a median age of 74 years were included; 15% were admitted to the ICU and 3.9% died in the hospital. In the multivariate analysis adjusted for confounding variables, the only marker significantly associated with the risk of dying or being admitted to the ICU was the NLR > 5 (OR: 3; CI95%: 1.5; 6). Similarly, the NLR > 5 was also associated to a lower probability of being discharged alive from the institution (SHR: 0.73; CI95%: 0.57; 0.94) and, therefore, a longer hospital stay. It was found that a neutrophil/lymphocyte ratio greater than 5 is a strong predictor of mortality or ICU admissions and a longer hospital stay in patients hospitalized with AECOPD.

The Role of Galectin-9 as Mediator of Atopic Dermatitis: Effect on Keratinocytes.

Galectin-9 (Gal-9) is a beta-galactoside-binding protein with a variety of biological functions related to immune response. However, in allergic diseases, its mechanism of action is not fully understood. This study evaluates the expression pattern of Gal-9 in patients with atopic dermatitis (AD), in ovalbumin (OVA)-induced experimental atopic dermatitis (AD) in mice, as well as its effect on human keratinocytes. The skin of OVA-immunized BALB/c mice was challenged with drops containing OVA on days 11, 14-18, and 21-24. HaCaT cells were cultured in the following experimental conditions: control (growth medium only) or stimulated with TNF-α/IFN-γ, or IL-4, or IL-17 with or without Gal-9 treatment. AD was characterized by increased levels of Gal-9 in mouse and human skin, especially in the epidermis, and with a marked influx of Gal-9 positive eosinophils and mast cells compared to the control group. Gal-9 showed an immunomodulatory effect on keratinocytes by decreasing the release of IL-6 by IL-4-stimulated keratinocytes or increasing the IL-6 and RANTES levels by IL-17- or TNF-α/IFN-γ-stimulated cells, respectively. Under IL-17, Gal-9 treatment also altered the proliferation rate of cells. Overall, increased levels of Gal-9 in AD skin contribute to the control of inflammatory response and the proliferative process of keratinocytes, suggesting this lectin as a relevant therapeutic target.

Neutrophil and Eosinophil DNA Extracellular Trap Formation: Lessons From Pathogenic Fungi.

Fungal infections represent a worldwide health problem. Fungal pathogens are responsible for a variety of conditions, including superficial diseases, allergic pathologies and potentially lethal invasive infections. Neutrophils and eosinophils have been implicated as effector cells in several pathologies. Neutrophils are major effector cells involved in the control of fungal infections and exhibit a plethora of antifungal mechanisms, such as phagocytosis, reactive oxygen species production, degranulation, extracellular vesicle formation, and DNA extracellular trap (ET) release. Eosinophils are polymorphonuclear cells classically implicated as effector cells in the pathogenesis of allergic diseases and helminthic infections, although their roles as immunomodulatory players in both innate and adaptive immunity are currently recognized. Eosinophils are also endowed with antifungal activities and are abundantly found in allergic conditions associated with fungal colonization and sensitization. Neutrophils and eosinophils have been demonstrated to release their nuclear and mitochondrial DNA in response to many pathogens and pro-inflammatory stimuli. ETs have been implicated in the killing and control of many pathogens, as well as in promoting inflammation and tissue damage. The formation of ETs by neutrophils and eosinophils has been described in response to pathogenic fungi. Here, we provide an overview of the mechanisms involved in the release of neutrophil and eosinophil ETs in response to fungal pathogens. General implications for understanding the formation of ETs and the roles of ETs in fungal infections are discussed.

Eosinophils increase macrophage ability to control intracellular Leishmania amazonensis infection via PGD2 paracrine activity in vitro.

Clinical and experimental studies have described eosinophil infiltration in Leishmania amazonensis infection sites, positioning eosinophils strategically adjacent to the protozoan-infected macrophages in cutaneous leishmaniasis. Here, by co-culturing mouse eosinophils with L. amazonensis-infected macrophages, we studied the impact of eosinophils on macrophage ability to regulate intracellular L. amazonensis infection. Eosinophils prevented the increase in amastigote numbers within macrophages by a mechanism dependent on a paracrine activity mediated by eosinophil-derived prostaglandin (PG) D2 acting on DP2 receptors. Exogenous PGD2 mimicked eosinophil-mediated effect on managing L. amazonensis intracellular infection by macrophages and therefore may function as a complementary tool for therapeutic intervention in L. amazonensis-driven cutaneous leishmaniasis.