RESUMO
Cystic echinococcosis is caused by the tissue-dwelling larva (hydatid) of Echinococcus granulosus sensu lato. A salient feature is that this larva is protected by the acellular laminated layer (LL). As the parasite grows, the LL sheds abundant particles that can accumulate in the parasite's vicinity. The potential of LL particles to induce inflammation in vivo has not been specifically analysed. It is not known how each of its two major components, namely highly glycosylated mucins and calcium inositol hexakisphosphate (InsP6) deposits, impacts inflammation induced by the LL as a whole. In this work, we show that LL particles injected intraperitoneally cause infiltration of eosinophils, neutrophils and monocytes/macrophages as well as the disappearance of resident (large peritoneal) macrophages. Strikingly, the absence of calcium InsP6 enhanced the recruitment of all the inflammatory cell types analysed. In contrast, oxidation of the mucin carbohydrates caused decreased recruitment of neutrophils. The carbohydrate-oxidised particles caused cell influx nonetheless, which may be explained by possible receptor-independent effects of LL particles on innate immune cells, as suggested by previous works from our group. In summary, LL particles can induce acute inflammatory cell recruitment partly dependent on its mucin glycans, and this recruitment is attenuated by the calcium InsP6 component.
Assuntos
Echinococcus granulosus , Ácido Fítico , Animais , Echinococcus granulosus/imunologia , Ácido Fítico/farmacologia , Ácido Fítico/metabolismo , Equinococose/imunologia , Equinococose/parasitologia , Inflamação , Neutrófilos/imunologia , Mucinas/metabolismo , Camundongos , Macrófagos/imunologia , Macrófagos/metabolismo , Eosinófilos/imunologia , Feminino , Larva/imunologiaRESUMO
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.
Assuntos
Angiotensina I , Lipopolissacarídeos , Pulmão , Ovalbumina , Fragmentos de Peptídeos , Animais , Angiotensina I/uso terapêutico , Angiotensina I/farmacologia , Angiotensina I/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/imunologia , Ovalbumina/imunologia , Camundongos , Masculino , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Camundongos Endogâmicos BALB C , Inflamação/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Eosinofilia/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologiaRESUMO
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.
Assuntos
Eosinófilos , Viroses , Humanos , Eosinófilos/imunologia , Eosinófilos/ultraestrutura , Viroses/imunologia , Viroses/patologia , Animais , Mitocôndrias/ultraestrutura , Mitocôndrias/imunologiaRESUMO
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.
Assuntos
Degranulação Celular , Eosinófilos , Vesículas Extracelulares , Humanos , Eosinófilos/imunologia , Eosinófilos/patologia , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Masculino , Eosinofilia/imunologia , Eosinofilia/patologia , Síndrome Hipereosinofílica/patologia , Síndrome Hipereosinofílica/imunologiaRESUMO
BACKGROUND: Little is known about the determinants of asthma among youth with high T helper 2 (Th2) immunity. We hypothesized that exposure to violence (ETV) and violence-related distress are associated with asthma in children and adolescents with high Th2 immunity. METHODS: We analyzed data from Puerto Ricans with high Th2 immunity aged 9-20 years in the Puerto Rico Genetics of Asthma and Lifestyle (PR-GOAL) and the Epigenetic Variation of Childhood Asthma in Puerto Ricans (EVA-PR) studies, and in a prospective study (PROPRA). High Th2-immunity was defined as ≥1 positive allergen-specific IgE and/or a total IgE ≥ 100 IU/mL and/or an eosinophil count ≥ 150 cells/µL. Asthma was defined as physician-diagnosed asthma and current wheeze. ETV and violence-related distress were assessed with the validated ETV Scale and Checklist of Children's Distress Symptoms (CCDS) questionnaires, respectively. RESULTS: In multivariable analyses, each 1-point increment in ETV score was significantly associated with 1.13-1.17 times increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.01), and each 1-point increment in CCDS score was significantly associated with 1.53-1.54 increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.03). Further, a persistently high ETV score was significantly associated with asthma in PROPRA (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.10-7.29). Similar results were obtained in a sensitivity analysis using an eosinophil count ≥ 300 cells/µL instead of ≥150 cells/µL to define high Th2 immunity. CONCLUSIONS: ETV during childhood is associated with increased risk of persistent or new-onset asthma in youth with high Th2 immunity.
Assuntos
Asma , Exposição à Violência , Adolescente , Criança , Humanos , Asma/epidemiologia , Asma/etiologia , Asma/imunologia , Exposição à Violência/etnologia , Hispânico ou Latino , Imunoglobulina E/análise , Imunoglobulina E/imunologia , Estudos Prospectivos , Porto Rico/epidemiologia , Violência , Células Th2/imunologia , Adulto Jovem , Eosinófilos/imunologia , Angústia PsicológicaRESUMO
The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-ß and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni, which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity.
Assuntos
Eosinófilos/imunologia , Imunidade/imunologia , Hepatopatias/imunologia , Fígado/imunologia , Doenças Negligenciadas/imunologia , Esquistossomose mansoni/imunologia , Animais , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/parasitologia , Feminino , Fibrose/imunologia , Fibrose/parasitologia , Granuloma/imunologia , Granuloma/parasitologia , Intestinos/imunologia , Intestinos/parasitologia , Fígado/parasitologia , Hepatopatias/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Doenças Negligenciadas/parasitologiaRESUMO
The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.
Assuntos
COVID-19/imunologia , Eosinófilos/imunologia , Plasmócitos/imunologia , SARS-CoV-2/fisiologia , Células Th1/imunologia , Idoso , Anticorpos Antivirais/sangue , Convalescença , Progressão da Doença , Feminino , Humanos , Imunidade Celular , Imunoglobulina G/sangue , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Knowledge about the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly regarding the function of eosinophils, has been steadily emerging recently. There exists controversy regarding the implications of eosinophils in the coronavirus disease 2019 (COVID-19)'s pathology. We report a retrospective cohort study including the comparison of leukocyte counts in COVID-19 patients, considering the outcomes of recovery (n = 59) and death (n = 60). Among the different types of leukocytes, the eosinophil counts were those that showed the greatest difference between recovered and deceased patients. Eosinopenia (eosinophil count < 0.01 × 109/L) was more frequently observed in deceased than recovered patients (p = 0.0012). The eosinophil counts more rapidly increased and showed a greater proportion over the course of the disease in the recovered than deceased patients. Furthermore, the estimated survival rate was greater in patients without eosinopenia than in patients with eosinopenia (p = 0.0070) during hospitalization. Importantly, recovered but not deceased patients showed high negative correlations of the eosinophils with the neutrophil-to-lymphocyte ratio (NLR) and neutrophil counts at Day 9 of the onset of clinical symptoms (p ≤ 0.0220). Our analysis suggests that eosinopenia may be associated with unfavorable disease outcomes and that the eosinophils have a beneficial function in COVID-19 patients, probably contributing by controlling the exacerbated inflammation induced by neutrophils.
Assuntos
COVID-19/sangue , COVID-19/virologia , Eosinófilos , Interações Hospedeiro-Patógeno , Contagem de Leucócitos , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , COVID-19/diagnóstico , COVID-19/imunologia , Comorbidade , Progressão da Doença , Eosinófilos/imunologia , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Leucócitos , Contagem de Linfócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Prognóstico , Estudos Retrospectivos , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
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.