RESUMO
Helminth-induced eosinophils accumulate around the parasite at the site of infection, or in parasite-damaged tissues well after the helminth has left the site. The role of helminth-elicited eosinophils in mediating parasite control is complex. While they may contribute to direct parasite-killing and tissue repair, their involvement in long-term immunopathogenesis is a concern. In allergic Siglec-FhiCD101hi, eosinophils are associated with pathology. Research has not shown if equivalent subpopulations of eosinophils are a feature of helminth infection. In this study, we demonstrate that lung migration of rodent hookworm Nippostrongylus brasiliensis (Nb) results in a long-term expansion of distinct Siglec-FhiCD101hi eosinophil subpopulations. Nb-elevated eosinophil populations in the bone marrow and circulation did not present this phenotype. Siglec-FhiCD101hi lung eosinophils exhibited an activated morphology including nuclei hyper-segmentation and cytoplasm degranulation. Recruitment of ST2+ ILC2s and not CD4+ T cells to the lungs was associated with the expansion of Siglec-FhiCD101hi eosinophils. This data identifies a morphologically distinct and persistent subset of Siglec-FhiCD101hi lung eosinophils induced following Nb infection. These eosinophils may contribute to long-term pathology following helminth infection.
Assuntos
Eosinófilos , Infecções por Uncinaria , Animais , Camundongos , Ancylostomatoidea , Imunidade Inata , Pulmão/parasitologia , Linfócitos , Nippostrongylus , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido SiálicoRESUMO
Type 2 Innate lymphoid cells (ILC2s) are tissue-resident immune cells activated by epithelial-derived alarmins upon tissue damage. They regulate immunity against helminth parasites and allergies by expressing type 2 immune response cytokines including IL-9, known to be critical for inducing and potentiating the immune response in such context. Although ILC2s are reported to be the main source of IL-9 in mice during N. brasiliensis infection, the mechanisms that regulate the expression of IL-9 in these cells are yet to be described. Recent studies have shown that in addition to cytokines, multiple molecules can differentially modulate the functions of ILC2s in various contexts both in vitro and in vivo. Among these stimuli are lipid mediators and neuropeptides, which activate the PKA pathway and have been associated with the regulation of type 2 immune cytokines. In this work we found that ILC2s in mice infected with N. brasiliensis can be classified into different groups based on the expression of IL-9 and ST2. These distinct populations were distributed in the lung and the small intestine. Through the development of an in vitro culture system, we sought to determine the stimuli that regulate the expression of these markers in ILC2s. We identified the alarmin IL-33 as being a key player for increased IL-9 expression. Additionally, we found the PKA pathway to be a dual regulator of ILC2 cells, working synergistically with IL-33 to enhance IL-9 production and capable of modulating proliferation and the expression of ILC2 markers. These data provide further evidence of a high heterogeneity between ILC2 subsets in a context dependent manner and calls for careful consideration when choosing the markers to identify these cells in vivo. Distinguishing ILC2 subsets and dissecting their mechanisms of activation is critical for a deeper understanding of the biology of these cells, allowing their manipulation for therapeutic purposes.
Assuntos
Imunidade Inata , Interleucina-33 , Animais , Citocinas , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Interleucina-9/genética , Linfócitos , CamundongosRESUMO
Innate lymphoid cells (ILCs) are the most recently described group of lymphoid subpopulations. These tissue-resident cells display a heterogeneity resembling that observed on different groups of T cells, hence their categorization as cytotoxic NK cells and helper ILCs type 1, 2 and 3. Each one of these groups is highly diverse and expresses different markers in a context-dependent manner. Type 2 innate lymphoid cells (ILC2s) are activated in response to helminth parasites and regulate the immune response. They are involved in the etiology of diseases associated with allergic responses as well as in the maintenance of tissue homeostasis. Markers associated with their identification differ depending on the tissue and model used, making the study and understanding of these cells a cumbersome task. This review compiles evidence for the heterogeneity of ILC2s as well as discussion and analyses of molecular markers associated with their identity, function, tissue-dependent expression, and how these markers contribute to the interaction of ILC2s with specific microenvironments to maintain homeostasis or respond to pathogenic challenges.
Assuntos
Antígenos de Diferenciação/análise , Subpopulações de Linfócitos/imunologia , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/patologia , Animais , Citocinas/metabolismo , Helmintíase/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Homeostase , Humanos , Imunofenotipagem , Inflamação , Intestinos/imunologia , Pulmão/imunologia , Subpopulações de Linfócitos/química , Camundongos , Nutrientes , Especificidade de Órgãos , Proteínas Proto-Oncogênicas c-kit/imunologia , Receptores de Superfície Celular/imunologia , Pele/imunologia , Fator de Células-Tronco/imunologiaRESUMO
Indoor environments contribute significantly to total human exposure to air pollutants, as people spend most of their time indoors. Household air pollution (HAP) resulting from cooking with polluting ("dirty") fuels, which include coal, kerosene, and biomass (wood, charcoal, crop residues, and animal manure) is a global environmental health problem. Indoor pollutants are gases, particulates, toxins, and microorganisms among others, that can have an impact especially on the health of children and adults through a combination of different mechanisms on oxidative stress and gene activation, epigenetic, cellular, and immunological systems. Air pollution is a major risk factor and contributor to morbidity and mortality from major chronic diseases. Children are significantly affected by the impact of the environment due to biological immaturity, prenatal and postnatal lung development. Poor air quality has been related to an increased prevalence of clinical manifestations of allergic asthma and rhinitis. Health professionals should increase their role in managing the exposure of children and adults to air pollution with better methods of care, prevention, and collective action. Interventions to reduce household pollutants may promote health and can be achieved with education, community, and health professional involvement.
RESUMO
Innate lymphoid cells (ILCs) are classified into distinct subsets termed ILC1, ILC2, and ILC3 cells. The existing literature lacks evidence identifying ILCs and their subsets in the human thymus but already demonstrates that they can exert several functions in regulating immune responses. Furthermore, it was already described that IgG's repertoires could modulate lymphocytes' maturation in the human thymus. Here we aimed to identify ILCs subsets in the human thymus and provide insight into the possible modulatory effect of purified IgG on these cells. Thymic tissues were obtained from 12 infants without an allergic background (non-atopic), and a literature-based peripheral ILCs staining protocol was used. Purified IgG was obtained from non-atopic individuals (n-At), atopic individuals reactive to allergens non-related to dust mites (nr-At), and atopic individuals reactive to the mite Dermatophagoides pteronyssinus (Derp-At). As with all tissues in which they have already been detected, thymic ILCs are rare, but we could detect viable ILCs in all tested tissues, which did not occur with the ILC1 subset. ILC2 and ILC3 NKp44+ subsets could be detected in all evaluated thymus, but ILC3 NKp44- subset could not. Next, we observed that Derp-At IgG could induce the expression of ILC2 phenotype, higher levels of IL-13, and lower levels of IL-4 when compared to IgG purified from non-atopic or non-related atopic (atopic to allergens excluding dust mites) individuals. These results contribute to the elucidation of human thymic ILCs and corroborate emerging evidence about IgG's premature effect on allergy development-related human lymphocytes' modulation.
RESUMO
INTRODUCTION: The interleukin-33/interleukin-13 pathway is involved in the immunopathology of liver fibrosis and recently characterized group 2 innate lymphoid cells (ILC2) were identified as profibrotic immune cells in the liver of mouse models. Our aim was to elucidate whether ILC2 might be present in human liver tissue and whether ILC2 contribute to liver fibrosis. MATERIALS AND METHODS: To identify ILC2 in liver tissue and blood, we purified mononuclear immune cells from needle biopsies, cirrhotic explant specimen, and paired peripheral blood samples. Cell suspensions were incubated with specific markers for ILC2 and analyzed by flow cytometry. The CD69 marker was included to assess the activation level of ILC2. In addition, we determined the IL-33 plasma level. RESULTS: Results were correlated with the METAVIR fibrotic score of patients enrolled in this study. We detected ILC2 in a higher percentage of CD45+ cells in liver tissue than in paired peripheral blood. The number of ILC2 was significantly increased in fibrotic tissue, but only slightly increased in paired peripheral blood. A higher percentage of CD69+ ILC2 was observed in fibrotic tissue, and this increase correlates positively with aggravation of liver fibrosis measured by fibrotic METAVIR score. A higher level of plasma IL-33 was only detected in samples obtained from cirrhotic patients. CONCLUSION: Our study indicates that ILC2 are present in the human liver and are activated in tissue contributing to the immunopathology of human liver fibrosis, independently of the etiology; which might be a potential new therapeutic target.
Assuntos
Imunidade Inata , Cirrose Hepática/imunologia , Fígado/imunologia , Linfócitos/imunologia , Adulto , Antígenos CD/sangue , Antígenos de Diferenciação de Linfócitos T/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Interleucina-33/sangue , Lectinas Tipo C/sangue , Antígenos Comuns de Leucócito/sangue , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Linfócitos/classificação , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Hookworm infections (Necator americanus or Ancylostoma duodenale) represent a major neglected tropical disease, affecting approximately 700 million people worldwide, and can cause severe morbidity due to the need for these worms to feed on host blood. N. brasiliensis and H. polygrus, both rodent parasites, are the two most commonly employed laboratory models of experimental hookworm infection. Both parasites evoke type 2 immune responses, and their use has been instrumental in generating fundamental insight into the molecular mechanisms of type-2 immunity and for understanding how the immune response can control parasite numbers. Here we provide a complete set of methods by which to investigate the natural progression of infection and the host immunological responses in the lung and intestine of H. polygyrus- and N. brasiliensis-infected mice. Detailed information is included about the most important parasitological and immunological measurements to perform at each time point. © 2017 by John Wiley & Sons, Inc.