RESUMEN
OBJECTIVES: We measured the production of cytokines, chemokines and antibodies involved in allergic responses and sCD23 levels during Schistosoma mansoni infection. METHODS: Individuals (n = 164) were selected using the ISAAC questionnaire and parasitological exams. The subjects were divided as follows: those infected individuals with allergy-related symptoms (A-I), those with allergy-related symptoms only (A-NI); those only infected (NA-I); and those non-infected individuals without allergy-related symptoms (NA-NI). We used supernatants from cell culture (mitogenic stimulation) to measure cytokine and chemokine levels using cytometric bead arrays. Serum levels of anti-Ascaris lumbricoides (Asc) and anti-Blomia tropicalis IgE were measured using ImmunoCAP, and sCD23 was measured using ELISA. RESULTS: Schistosoma mansoni infection was associated with a lower risk of allergy-related symptoms. In A-I, there were higher levels of TNF-α, IL-10, IL-6, IFN-γ and CXCL8 than in NA-NI group, with TNF-α and IL-6 also at higher levels compared to A-NI group. Levels of IL-6, CXCL8, total and anti-Asc IgE, as well as the numbers of eosinophils, were higher in NA-I than in NA-NI, and the antibodies were also lower in A-NI than in NA-I group. In AI and NA-I, there was less production of CCL2 than in NA-NI. There were no differences in the levels of IL-2, IL-4, IL-17, CCL5, sCD23 and anti-Blomia IgE. CONCLUSIONS: Patients with allergy-related symptoms and infected (simultaneously) had higher levels of IL-10; due to the infection, there was increased production of IL-6 and CXCL8 and less CCL2. These data may characterize deviation to Th1 or attenuation of the Th2 response in allergy sufferers in areas endemic for schistosomiasis.
Asunto(s)
Anticuerpos/inmunología , Quimiocinas/inmunología , Citocinas/inmunología , Hipersensibilidad Respiratoria/parasitología , Esquistosomiasis mansoni/inmunología , Adolescente , Adulto , Animales , Anticuerpos/sangre , Anticuerpos Antihelmínticos/sangre , Anticuerpos Antihelmínticos/inmunología , Brasil/epidemiología , Quimiocina CCL2/inmunología , Quimiocinas/sangre , Niño , Preescolar , Citocinas/sangre , Femenino , Humanos , Inmunoglobulina E , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We measured the effect of Rho-kinase on inflammation and mucus hypersecretion in the airways of mouse models of asthma. Additionally, we aimed to determine if these effects were the result of JNK 1/2-AP1 pathway inhibition.We sensitized and challenged female C57BL/6 mice using house dust mites (HDM) followed by treatment with an inhibitor of Rho-kinase. Lung tissue was harvested to evaluate inflammation and mucus secretion in the airways of asthma mice. Cytokine expression in broncho-alveolar lavage fluid (BALF) was established by ELISA and airway responsiveness, and was determined by the invasive lung function test. JNK1/2, p-JNK1/2, AP-1, and p-AP-1 protein expression was determined by Western blot analysis. Asthma model mice that were treated with Rho-kinase inhibitor showed a significantly decrease in inflammation score, inflammatory cells, and airway responsiveness. Additionally, we found that IL-13 expressions in BALF and mucus secretion were decreased in HDM-challenged mice treated with Rho-kinase inhibitor. Furthermore, Rho-kinase inhibitor treatment decreased the expression of JNK1/2 and AP-1 phosphorylation. Our findings indicated that the Rho-kinase inhibitor decreased HDM-induced mucus secretion as well as airway inflammation in asthma mice through regulation of the JNK1/2-AP-1 pathway.
Asunto(s)
Regulación hacia Abajo , Inflamación/patología , Interleucina-13/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Moco/metabolismo , Transducción de Señal , Factor de Transcripción AP-1/metabolismo , Quinasas Asociadas a rho/antagonistas & inhibidores , Animales , Asma/complicaciones , Asma/parasitología , Asma/patología , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Femenino , Ratones Endogámicos C57BL , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Pyroglyphidae/fisiología , Hipersensibilidad Respiratoria/complicaciones , Hipersensibilidad Respiratoria/parasitología , Transducción de Señal/efectos de los fármacos , Quinasas Asociadas a rho/metabolismoRESUMEN
BACKGROUND: In previous studies, we suggested that Acanthamoeba is a new aero-allergen and that patients who showed positive results for the skin-prick test response to Acanthamoeba cross-reacted with several pollen allergens. Additionally, patients with common antibodies reacted to the 13-15 kDa Acanthamoeba unknown allergen. OBJECTIVE: We examined whether profilin of Acanthamoeba is a human airway allergic agent because of its molecular weight. METHODS: We expressed recombinant Ac-PF (rAc-PF) protein using an Escherichia coli expression system and evaluated whether Ac-PF is an airway allergic agent using an allergic airway inflammation animal model. RESULTS: Airway hyperresponsiveness was increased in rAc-PF-inoculated mice. The number of eosinophils and levels of Th2 cytokines, interleukin (IL)-4, IL-5, and IL-13 were increased in the bronchial alveolar lavage fluid of rAc-PF-treated mice. The lungs of the rAc-PF-treated mice group showed enhanced mucin production and metaplasia of lung epithelial cells and goblet cells. CONCLUSION: In this study, we demonstrated that rAc-PF may be an allergen in Acanthamoeba, but further studies needed to identify the mechanisms of allergenic reactions induced by Ac-PF.
Asunto(s)
Acanthamoeba/inmunología , Amebiasis/inmunología , Profilinas/inmunología , Hipersensibilidad Respiratoria/inmunología , Acanthamoeba/genética , Amebiasis/genética , Amebiasis/parasitología , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Interleucina-13/genética , Interleucina-13/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Pulmón/inmunología , Pulmón/parasitología , Ratones , Ratones Endogámicos C57BL , Profilinas/genética , Ratas , Ratas Wistar , Hipersensibilidad Respiratoria/genética , Hipersensibilidad Respiratoria/parasitologíaRESUMEN
Ascaris lumbricoides (roundworm) is the most common helminth infection globally and a cause of lifelong morbidity that may include allergic airway disease, an asthma phenotype. We hypothesize that Ascaris larval migration through the lungs leads to persistent airway hyperresponsiveness (AHR) and type 2 inflammatory lung pathology despite resolution of infection that resembles allergic airway disease. Mice were infected with Ascaris by oral gavage. Lung AHR was measured by plethysmography and histopathology with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stains, and cytokine concentrations were measured by using Luminex Magpix. Ascaris-infected mice were compared to controls or mice with allergic airway disease induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Ascaris-infected mice developed profound AHR starting at day 8 postinfection (p.i.), peaking at day 12 p.i. and persisting through day 21 p.i., despite resolution of infection, which was significantly increased compared to controls and OVA/OVA mice. Ascaris-infected mice had a robust type 2 cytokine response in both the bronchoalveolar lavage (BAL) fluid and lung tissue, similar to that of the OVA/OVA mice, including interleukin-4 (IL-4) (P < 0.01 and P < 0.01, respectively), IL-5 (P < 0.001 and P < 0.001), and IL-13 (P < 0.001 and P < 0.01), compared to controls. By histopathology, Ascaris-infected mice demonstrated early airway remodeling similar to, but more profound than, that in OVA/OVA mice. We found that Ascaris larval migration causes significant pulmonary damage, including AHR and type 2 inflammatory lung pathology that resembles an extreme form of allergic airway disease. Our findings indicate that ascariasis may be an important cause of allergic airway disease in regions of endemicity.
Asunto(s)
Ascariasis/fisiopatología , Hipersensibilidad/parasitología , Pulmón/patología , Hipersensibilidad Respiratoria/parasitología , Animales , Ascariasis/inmunología , Ascaris/patogenicidad , Líquido del Lavado Bronquioalveolar/inmunología , Modelos Animales de Enfermedad , Femenino , Interleucina-13/inmunología , Interleucina-4/inmunología , Interleucina-5/inmunología , Larva/patogenicidad , Pulmón/parasitología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , Células Th2/inmunologíaRESUMEN
It is anticipated that bioactive fragments of the extracellular matrix (matrikines) can influence the development and progression of chronic diseases. The enzyme leukotriene A4 hydrolase (LTA4H) mediates opposing proinflammatory and anti-inflammatory activities, through the generation of leukotriene B4 (LTB4) and degradation of proneutrophilic matrikine Pro-Gly-Pro (PGP), respectively. We show that abrogation of LTB4 signaling ameliorated inflammation and airway hyperresponsiveness (AHR) in a murine asthma model, yet global loss of LTA4H exacerbated AHR, despite the absence of LTB4 This exacerbated AHR was attributable to a neutrophil-independent capacity of PGP to promote pathological airway epithelial remodeling. Thus, we demonstrate a disconnect between airway inflammation and AHR and the ability of a matrikine to promote an epithelial remodeling phenotype that negatively affects lung function. Subsequently, we show that substantial quantities of PGP are detectable in the sputum of moderate-severe asthmatics in two distinct cohorts of patients. These studies have implications for our understanding of remodeling phenotypes in asthma and may rationalize the failure of LTA4H inhibitors in the clinic.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Células Epiteliales/metabolismo , Matriz Extracelular/metabolismo , Hipersensibilidad Respiratoria/fisiopatología , Resistencia de las Vías Respiratorias , Animales , Asma/complicaciones , Asma/inmunología , Asma/patología , Asma/fisiopatología , Bronquios/patología , Recuento de Células , Modelos Animales de Enfermedad , Epóxido Hidrolasas/deficiencia , Epóxido Hidrolasas/metabolismo , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/inmunología , Hipersensibilidad/patología , Hipersensibilidad/fisiopatología , Inflamación/patología , Mediadores de Inflamación/metabolismo , Ratones Endogámicos C57BL , Moco/metabolismo , Neutrófilos/metabolismo , Oligopéptidos/metabolismo , Prolina/análogos & derivados , Prolina/metabolismo , Pyroglyphidae/fisiología , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/parasitología , Hipersensibilidad Respiratoria/patología , Esputo/metabolismo , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
The "hygiene hypothesis" is a theory try to explain the dramatic increases in the prevalence of autoimmune and allergic diseases over the past two to three decades in developed countries. According to this theory, reduced exposure to parasites and microorganisms in childhood is the main cause for the increased incidences of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. In this study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found that S. japonicum infection downregulated airway hyperresponsiveness. The infiltrating cells, Th17 and Th2 effector cytokines in the bronchoalveolar lavage (BAL) fluids and lungs were significantly reduced in the infected mice. Our findings indicated that S. japonicum infection was able to effectively inhibit host's allergic airway inflammation, which may be related to the upregulated Treg cells upon infection. To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms.
Asunto(s)
Inflamación/inmunología , Pyroglyphidae/inmunología , Hipersensibilidad Respiratoria/inmunología , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/inmunología , Animales , Asma/sangre , Asma/inmunología , Asma/parasitología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/genética , Citocinas/inmunología , Citocinas/metabolismo , Regulación hacia Abajo/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Interacciones Huésped-Parásitos/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Inflamación/sangre , Inflamación/parasitología , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Neutrófilos/metabolismo , Pyroglyphidae/fisiología , Hipersensibilidad Respiratoria/sangre , Hipersensibilidad Respiratoria/parasitología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Schistosoma japonicum/fisiología , Esquistosomiasis Japónica/parasitología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
IL-23 has been postulated to be a critical mediator contributing to various inflammatory diseases. Dermatophagoides pteronyssinus (Der p) is one of the most common inhalant allergens. However, the role of IL-23 in Der p-induced mouse asthma model is not well understood, particularly with regard to the development of allergic sensitization in the airways. The objective of this study was to evaluate roles of IL-23 in Der p sensitization and asthma development. BALB/c mice were repeatedly administered Der p intranasally to develop Der p allergic sensitization and asthma. After Der p local administration, changes in IL-23 expression were examined in lung tissues and primary epithelial cells. Anti-IL-23p19 antibody was given during the Der p sensitization period, and its effects were examined. Effects of anti-IL-23p19 antibody at bronchial epithelial levels were also examined in vitro. The expression of IL-23 at bronchial epithelial layers was increased after Der p local administration in mouse. In Der p-induced mouse models, anti-IL-23p19 antibody treatment during allergen sensitization significantly diminished Der p allergic sensitization and several features of allergic asthma including the production of Th2 cytokines and the population of type 2 innate lymphoid cells in lungs. The activation of dendritic cells in lung-draining lymph nodes was also reduced by anti-IL-23 treatment. In murine lung alveolar type II-like epithelial cell line (MLE-12) cells, IL-23 blockade prevented cytokine responses to Der p stimulation, such as IL-1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-33, and also bone marrow-derived dendritic cell activation. In conclusion, IL-23 is another important bronchial epithelial cell-driven cytokine which may contribute to the development of house dust mite allergic sensitization and asthma.
Asunto(s)
Asma/inmunología , Bronquios/patología , Células Epiteliales/metabolismo , Hipersensibilidad/patología , Inmunización , Interleucina-23/metabolismo , Animales , Anticuerpos/farmacología , Asma/complicaciones , Asma/parasitología , Asma/patología , Células de la Médula Ósea/patología , Recuento de Células , Células Cultivadas , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Dermatophagoides pteronyssinus/efectos de los fármacos , Dermatophagoides pteronyssinus/fisiología , Modelos Animales de Enfermedad , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Femenino , Hipersensibilidad/complicaciones , Hipersensibilidad/inmunología , Hipersensibilidad/parasitología , Inmunidad Innata/efectos de los fármacos , Inmunoglobulina G/metabolismo , Interleucina-13/metabolismo , Interleucina-1alfa/metabolismo , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Ratones Endogámicos BALB C , Fenotipo , Neumonía/inmunología , Neumonía/parasitología , Neumonía/patología , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/parasitología , Hipersensibilidad Respiratoria/patología , Especificidad de la Especie , Células Th2/efectos de los fármacos , Células Th2/metabolismoRESUMEN
Strongyloidiasis is a neglected chronic nematode infection, in which the control of autoinfection rate and severity of disease is dependent on type 2 immune responses. Strongyloides also causes Th2 responses in the lung of infected animals and changes in airway function, including airway hyperresponsiveness (AHR). Mechanisms of AHR during Strongyloides venezuelensis infection are not entirely known, and we investigate here the role of IL-4, eosinophils, and IL-33/ST2. AHR was evaluated in infected mice by determining changes in lung function after increasing doses of methacholine. Balb/C, but no C57Bl/6, mice developed AHR, tissue eosinophilia, and increased local IL-4 and IL-5 production. Functional changes peaked at day 4 and 7, after the larva had left the lungs. AHR was clearly dependent on IL-4 but not on eosinophils, as evaluated by experiments in IL-4 and Gata-1-deficient mice. Experiments in ST2-deficient mice showed that this pathway was not needed for induction of AHR but was necessary for the maintenance of AHR and for Th2 responses in the lung. These studies clearly show a crucial role for IL-4 in the induction of AHR following S. venezuelensis infection and for IL-33/ST2 in maintaining AHR and lung Th2 responses.
Asunto(s)
Eosinófilos/inmunología , Proteína 1 Similar al Receptor de Interleucina-1/inmunología , Interleucina-33/inmunología , Interleucina-4/inmunología , Hipersensibilidad Respiratoria/inmunología , Strongyloides/inmunología , Estrongiloidiasis/inmunología , Alérgenos/inmunología , Animales , Eosinofilia/inmunología , Eosinofilia/parasitología , Factor de Transcripción GATA1/genética , Proteína 1 Similar al Receptor de Interleucina-1/genética , Interleucina-4/biosíntesis , Interleucina-4/genética , Interleucina-5/biosíntesis , Interleucina-5/inmunología , Recuento de Leucocitos , Pulmón/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Hipersensibilidad Respiratoria/parasitología , Estrongiloidiasis/parasitología , Células Th2/inmunologíaRESUMEN
Protein S-glutathionylation (PSSG) is an oxidant-induced post-translational modification of protein cysteines that impacts structure and function. The oxidoreductase glutaredoxin-1 (Glrx1) under physiological conditions catalyzes deglutathionylation and restores the protein thiol group. The involvement of Glrx1/PSSG in allergic inflammation induced by asthma-relevant allergens remains unknown. In the present study, we examined the impact of genetic ablation of Glrx1 in the pathogenesis of house dust mite (HDM)-induced allergic airways disease in mice. Wild-type (WT) or Glrx1(-/-) mice were instilled intranasally with HDM on 5 consecutive days for 3 weeks. As expected, overall PSSG was increased in Glrx1(-/-) HDM mice as compared with WT animals. Total cells in bronchoalveolar lavage fluid were similarly increased in HDM-treated WT and Glrx1(-/-) mice. However, in response to HDM, mice lacking Glrx1 demonstrated significantly more neutrophils and macrophages but fewer eosinophils as compared with HDM-exposed WT mice. mRNA expression of the Th2-associated cytokines IL-13 and IL-6, as well as mucin-5AC (Muc5ac), was significantly attenuated in Glrx1(-/-) HDM-treated mice. Conversely, mRNA expression of IFN-γ and IL-17A was increased in Glrx1(-/-) HDM mice compared with WT littermates. Restimulation of single-cell suspensions isolated from lungs or spleens with HDM resulted in enhanced IL-17A and decreased IL-5 production in cells derived from inflamed Glrx1(-/-) mice compared with WT animals. Finally, HDM-induced tissue damping and elastance were significantly attenuated in Glrx1(-/-) mice compared with WT littermates. These results demonstrate that the Glrx1-PSSG axis plays a pivotal role in HDM-induced allergic airways disease in association with enhanced type 2 inflammation and restriction of IFN-γ and IL-17A.
Asunto(s)
Glutarredoxinas/metabolismo , Hipersensibilidad/patología , Hipersensibilidad/parasitología , Pulmón/patología , Pulmón/parasitología , Pyroglyphidae/fisiología , Animales , Citocinas/genética , Citocinas/metabolismo , Glutatión/metabolismo , Hiperplasia , Hipersensibilidad/sangre , Hipersensibilidad/complicaciones , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Ratones Endogámicos BALB C , Moco/metabolismo , Neumonía/sangre , Neumonía/complicaciones , Neumonía/parasitología , Neumonía/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Hipersensibilidad Respiratoria/sangre , Hipersensibilidad Respiratoria/parasitología , Hipersensibilidad Respiratoria/patología , Hipersensibilidad Respiratoria/fisiopatología , Mecánica Respiratoria , Células Th2/inmunologíaRESUMEN
Most patients with allergic asthma are sensitized to house dust mite (HDM). The allergenicity of HDM largely depends on disruption of the integrity and proinflammatory activation of the airway epithelium. In this study, we hypothesized that Pim1 kinase activity attenuates HDM-induced asthma by preserving airway epithelial integrity. The effects of Pim1 kinase activity on barrier function and release of the proinflammatory mediators IL-1α and CCL20 were studied in vitro in 16HBE and primary bronchial epithelial cells (PBECs). Pim1-proficient and -deficient mice were exposed to a HDM-driven model of allergic asthma, and airway hyperresponsiveness (AHR) was measured upon methacholine challenge. Airway inflammation and proinflammatory mediators in lung tissue and BAL fluid were determined. We observed that inhibition of Pim1 kinase prolongs the HDM-induced loss of barrier function in 16HBE cells and sensitizes PBECs to HDM-induced barrier dysfunction. Additionally, inhibition of Pim1 kinase increased the HDM-induced proinflammatory activity of 16HBE cells as measured by IL-1α secretion. In line herewith, HDM exposure induced an enhanced production of the proinflammatory chemokines CCL17 and CCL20 in Pim1-deficient mice compared with wild-type controls. While we observed a marked increase in eosinophilic and neutrophilic granulocytes as well as mucus cell metaplasia and AHR to methacholine in mice exposed to HDM, these parameters were independent of Pim1 kinase activity. In contrast, levels of the Th2-cytokines IL-5 and IL-10 were significantly augmented in HDM-treated Pim1-deficient mice. Taken together, our study shows that Pim1 kinase activity maintains airway epithelial integrity and protects against HDM-induced proinflammatory activation of the airway epithelium.
Asunto(s)
Bronquios/patología , Células Epiteliales/enzimología , Células Epiteliales/parasitología , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Pyroglyphidae/fisiología , Adulto , Anciano , Animales , Líquido del Lavado Bronquioalveolar/citología , Línea Celular , Quimiocinas/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Inflamación/parasitología , Inflamación/patología , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Neumonía/patología , Proteínas Proto-Oncogénicas c-pim-1/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-pim-1/deficiencia , Hipersensibilidad Respiratoria/enzimología , Hipersensibilidad Respiratoria/parasitología , Hipersensibilidad Respiratoria/patología , Células Th2/inmunología , Adulto JovenRESUMEN
BACKGROUND: The Hygiene Hypothesis proposes that infection exposure protects against inflammatory conditions. Helminths possess allergen-like molecules and may specifically modulate allergy-related immunological pathways to inhibit responses which protect against them. Mass drug administration is recommended for helminth-endemic communities to control helminth-induced pathology, but may also result in increased rates of inflammation-mediated diseases in resource-poor settings. Immunological studies integrated with implementation of helminth control measures may elucidate how helminth elimination contributes to ongoing epidemics of inflammatory diseases. We present the design of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA), a cluster-randomised trial evaluating the risks and benefits of intensive versus standard anthelminthic treatment for allergy-related diseases and other health outcomes. METHODS/DESIGN: The setting is comprised of island fishing communities in Mukono district, Uganda. Twenty-six communities have been randomised in a 1:1 ratio to receive standard or intensive anthelminthic intervention for a three-year period. Baseline characteristics were collected immediately prior to intervention rollout, commenced in February 2013. Primary outcomes are reported wheeze in the past 12 months and atopy (skin prick test response and allergen-specific immunoglobulin (asIg) E concentration). Secondary outcomes are visible flexural dermatitis, helminth infections, haemoglobin, growth parameters, hepatosplenomegaly, and responses to vaccine antigens. The trial provides a platform for in-depth analysis of clinical and immunological consequences of the contrasting interventions. DISCUSSION: The baseline survey has been completed successfully in a challenging environment. Baseline characteristics were balanced between trial arms. Prevalence of Schistosoma mansoni, hookworm, Strongyloides stercoralis and Trichuris trichiura was 52%, 23%, 13%, and 12%, respectively; 31% of Schistosoma mansoni infections were heavy (>400 eggs/gram). The prevalence of reported wheeze and positive skin prick test to any allergen was 5% and 20%, respectively. Respectively, 77% and 87% of participants had Dermatophagoides- and German cockroach-specific IgE above 0.35 kUA/L. These characteristics suggest that the LaVIISWA study will provide an excellent framework for investigating beneficial and detrimental effects of worms and their treatment, and the mechanisms of such effects. TRIAL REGISTRATION: This trial was registered with Current Controlled Trials (identifier: ISRCTN47196031) on 7 September 2012.
Asunto(s)
Albendazol/administración & dosificación , Antihelmínticos/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Praziquantel/administración & dosificación , Hipersensibilidad Respiratoria/tratamiento farmacológico , Esquistosomiasis mansoni/tratamiento farmacológico , Estrongiloidiasis/tratamiento farmacológico , Tricuriasis/tratamiento farmacológico , Albendazol/efectos adversos , Animales , Antihelmínticos/efectos adversos , Biomarcadores/sangre , Protocolos Clínicos , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Dermatitis Atópica/parasitología , Esquema de Medicación , Hemoglobinas/metabolismo , Interacciones Huésped-Parásitos , Humanos , Inmunoglobulina E/sangre , Pruebas Intradérmicas , Praziquantel/efectos adversos , Proyectos de Investigación , Hipersensibilidad Respiratoria/diagnóstico , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/parasitología , Ruidos Respiratorios/efectos de los fármacos , Ruidos Respiratorios/inmunología , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/inmunología , Schistosoma mansoni/patogenicidad , Esquistosomiasis mansoni/diagnóstico , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/parasitología , Strongyloides stercoralis/efectos de los fármacos , Strongyloides stercoralis/inmunología , Strongyloides stercoralis/patogenicidad , Estrongiloidiasis/diagnóstico , Estrongiloidiasis/inmunología , Estrongiloidiasis/parasitología , Factores de Tiempo , Resultado del Tratamiento , Tricuriasis/diagnóstico , Tricuriasis/inmunología , Tricuriasis/parasitología , Trichuris/efectos de los fármacos , Trichuris/inmunología , Trichuris/patogenicidad , UgandaRESUMEN
B cells have been described as having the capacity to regulate cellular immune responses and suppress inflammatory processes. One such regulatory B-cell population is defined as IL-10-producing CD19(+) CD1d(hi) cells. Previous work has identified an expansion of these cells in mice infected with the helminth, Schistosoma mansoni. Here, microarray analysis of CD19(+) CD1d(hi) B cells from mice infected with S. mansoni demonstrated significantly increased Tlr7 expression, while CD19(+) CD1d(hi) B cells from uninfected mice also demonstrated elevated Tlr7 expression. Using IL-10 reporter, Il10(-/-) and Tlr7(-/-) mice, we formally demonstrate that TLR7 ligation of CD19(+) CD1d(hi) B cells increases their capacity to produce IL-10. In a mouse model of allergic lung inflammation, the adoptive transfer of TLR7-elicited CD19(+) CD1d(hi) B cells reduced airway inflammation and associated airway hyperresponsiveness. Using DEREG mice to deplete FoxP3(+) T regulatory cells in allergen-sensitized mice, we show that that TLR7-elicited CD19(+) CD1d(hi) B cells suppress airway hyperresponsiveness via a T regulatory cell dependent mechanism. These studies identify that TLR7 stimulation leads to the expansion of IL-10-producing CD19(+) CD1d(hi) B cells, which can suppress allergic lung inflammation via T regulatory cells.
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Linfocitos B/inmunología , Linfocitos B/metabolismo , Neumonía/inmunología , Neumonía/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Receptor Toll-Like 7/metabolismo , Animales , Antígenos CD19/metabolismo , Antígenos CD1d/metabolismo , Modelos Animales de Enfermedad , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/metabolismo , Interleucina-10/biosíntesis , Ratones , Ratones Noqueados , Ovalbúmina/efectos adversos , Neumonía/parasitología , Unión Proteica , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/parasitología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/metabolismo , Regulación hacia ArribaRESUMEN
Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES) proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25) in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF) inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease.
Asunto(s)
Acanthamoeba/enzimología , Péptido Hidrolasas/metabolismo , Receptor PAR-2/metabolismo , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/parasitología , Acanthamoeba/inmunología , Amebiasis/genética , Amebiasis/inmunología , Amebiasis/metabolismo , Amebiasis/parasitología , Animales , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/inmunología , Asma/inmunología , Asma/metabolismo , Asma/parasitología , Línea Celular , Quimiocinas/biosíntesis , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunoglobulina E/inmunología , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/parasitología , Ratones , Receptor PAR-2/genética , Hipersensibilidad Respiratoria/genética , Hipersensibilidad Respiratoria/inmunología , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
OBJETIVO: Uma elevada incidência de enteroparasitoses é encontrada em regiões urbanas do nordeste brasileiro. As infecções por Giardia lamblia têm sido relacionadas com aumento da prevalência de alergias cutâneas e gastrointestinais. Contudo, ainda existe pouca informação sobre a associação entre a giardíase e doenças alérgicas das vias aéreas. Diante disso, o presente estudo se propôs a verificar a relação entre a infecção por G. lamblia em crianças de área urbana e reatividade alérgica respiratória. MÉTODOS: O estudo incluiu 110 pacientes, de ambos os sexos e idades, entre 5 e 15 anos. Os pacientes foram submetidos a questionários de avaliação dos sintomas clínicos, testes cutâneos de leitura imediata e exames coproparasitológicos e sorológicos. RESULTADOS: Foi verificada uma frequência elevada de crianças infectadas por G. lamblia (45%, 50/110). A infecção pelo protozoário não foi associada com maior risco de alergias respiratórias (p = 0,075), elevação de IgE total (p = 0,701), IgE específica (p = 0,250) ou teste cutâneo positivo para diferentes alérgenos ambientais (p = 0,239). CONCLUSÃO: O estudo demonstrou que a presença dos sintomas de asma, atopia cutânea e marcadores sorológicos não foram associados com a presença de infecção pela G. lamblia nessa amostra de crianças.
OBJECTIVES: There is a high incidence of intestinal parasite infection in urban areas in the Northeast of Brazil. Giardia lamblia infections have been associated with increased prevalence of cutaneous allergies and gastrointestinal disorders. However, little is known about the relationship between giardiasis and allergic diseases of the airways. The present study aimed to investigate the possible association between respiratory allergic diseases and infections by G. lamblia in children from urban areas. METHODS: This study recruited 110 patients of both sexes aged 5-15 years. Patients were administered a questionnaire evaluating clinical symptoms and were given skin tests, parasite tests and serum tests. RESULTS: A high incidence of G. lamblia was observed (45%, 50/110). Infections by this protozoan were not associated with increased risk of respiratory allergy (p = 0.075), high total IgE levels (p = 0.701), positive specific IgE tests (p = 0.250), or positive skin tests for a range of environmental allergens (p = 0.239). CONCLUSION: This study demonstrated that symptoms of asthma, skin allergy and serum markers were not associated with G. lamblia infections in this sample of children from urban areas.
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Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Giardia lamblia/aislamiento & purificación , Giardiasis/epidemiología , Inmunoglobulina E/inmunología , Hipersensibilidad Respiratoria/inmunología , Brasil/epidemiología , Estudios Transversales , Giardiasis/complicaciones , Inmunoglobulina E/sangre , Prevalencia , Hipersensibilidad Respiratoria/epidemiología , Hipersensibilidad Respiratoria/parasitología , Pruebas Cutáneas , Encuestas y Cuestionarios , Población Urbana/estadística & datos numéricosRESUMEN
OBJECTIVES: There is a high incidence of intestinal parasite infection in urban areas in the Northeast of Brazil. Giardia lamblia infections have been associated with increased prevalence of cutaneous allergies and gastrointestinal disorders. However, little is known about the relationship between giardiasis and allergic diseases of the airways. The present study aimed to investigate the possible association between respiratory allergic diseases and infections by Giardia lamblia in children from urban areas. METHODS: This study recruited 110 patients of both sexes aged 5-15 years. Patients were administered a questionnaire evaluating clinical symptoms and were given skin tests, parasite tests and serum tests. RESULTS: A high incidence of Giardia lamblia was observed (45%, 50/110). Infections by this protozoan were not associated with increased risk of respiratory allergy (p = 0.075), high total IgE levels (p = 0.701), positive specific IgE tests (p = 0.250), or positive skin tests for a range of environmental allergens (p = 0.239). CONCLUSION: This study demonstrated that symptoms of asthma, skin allergy and serum markers were not associated with Giardia lamblia infections in this sample of children from urban areas.
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Giardia lamblia/aislamiento & purificación , Giardiasis/epidemiología , Inmunoglobulina E/inmunología , Hipersensibilidad Respiratoria/inmunología , Adolescente , Brasil/epidemiología , Niño , Preescolar , Estudios Transversales , Femenino , Giardiasis/complicaciones , Humanos , Inmunoglobulina E/sangre , Masculino , Prevalencia , Hipersensibilidad Respiratoria/epidemiología , Hipersensibilidad Respiratoria/parasitología , Pruebas Cutáneas , Encuestas y Cuestionarios , Población Urbana/estadística & datos numéricosRESUMEN
Allergic airways disease is a consequence of a Th2 response to an allergen leading to a series of manifestations such as production of allergen-specific IgE, inflammatory infiltrates in the airways, and airway hyper-reactivity (AHR). Several strategies have been reported for tolerance induction to allergens leading to protection from allergic airways disease. We now show that CD4 blockade at the time of house dust mite sensitization induces antigen-specific tolerance in mice. Tolerance induction is robust enough to be effective in pre-sensitized animals, even in those where AHR was pre-established. Tolerant mice are protected from airways eosinophilia, Th2 lung infiltration, and AHR. Furthermore, anti-CD4 treated mice remain immune competent to mount immune responses, including Th2, to unrelated antigens. Our findings, therefore, describe a strategy for tolerance induction potentially applicable to other immunogenic proteins besides allergens.
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Tolerancia Inmunológica/inmunología , Pyroglyphidae/inmunología , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/prevención & control , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Antígenos Dermatofagoides/inmunología , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/parasitología , Hiperreactividad Bronquial/prevención & control , Antígenos CD4/inmunología , Epítopos/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Inmunización , Inmunocompetencia/efectos de los fármacos , Inmunocompetencia/inmunología , Ratones , Ratones Endogámicos BALB C , Neumonía/complicaciones , Neumonía/inmunología , Pyroglyphidae/efectos de los fármacos , Hipersensibilidad Respiratoria/complicaciones , Hipersensibilidad Respiratoria/parasitologíaRESUMEN
In the murine model of Cryptococcus neoformans infection Th1 (IL-12/IFN-gamma) and Th17 (IL-23/IL-17) responses are associated with protection, whereas an IL-4-dependent Th2 response exacerbates disease. To investigate the role of the Th2 cytokine IL-13 during pulmonary infection with C. neoformans, IL-13-overexpressing transgenic (IL-13Tg(+)), IL-13-deficient (IL-13(-/-)), and wild-type (WT) mice were infected intranasally. Susceptibility to C. neoformans infection was found when IL-13 was induced in WT mice or overproduced in IL-13Tg(+) mice. Infected IL-13Tg(+) mice had a reduced survival time and higher pulmonary fungal load as compared with WT mice. In contrast, infected IL-13(-/-) mice were resistant and 89% of these mice survived the entire period of the experiment. Ag-specific production of IL-13 by susceptible WT and IL-13Tg(+) mice was associated with a significant type 2 cytokine shift but only minor changes in IFN-gamma production. Consistent with enhanced type 2 cytokine production, high levels of serum IgE and low ratios of serum IgG2a/IgG1 were detected in susceptible WT and IL-13Tg(+) mice. Interestingly, expression of IL-13 by susceptible WT and IL-13Tg(+) mice was associated with reduced IL-17 production. IL-13 was found to induce formation of alternatively activated macrophages expressing arginase-1, macrophage mannose receptor (CD206), and YM1. In addition, IL-13 production led to lung eosinophilia, goblet cell metaplasia and elevated mucus production, and enhanced airway hyperreactivity. This indicates that IL-13 contributes to fatal allergic inflammation during C. neoformans infection.
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Criptococosis/inmunología , Citocinas/biosíntesis , Interleucina-13/fisiología , Enfermedades Pulmonares Fúngicas/inmunología , Enfermedades Pulmonares Fúngicas/patología , Macrófagos Alveolares/inmunología , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/patología , Animales , Anticuerpos Antifúngicos/biosíntesis , Anticuerpos Antifúngicos/clasificación , Cryptococcus neoformans/inmunología , Femenino , Isotipos de Inmunoglobulinas/biosíntesis , Inflamación/inmunología , Inflamación/parasitología , Inflamación/patología , Interleucina-13/biosíntesis , Interleucina-13/deficiencia , Interleucina-13/genética , Enfermedades Pulmonares Fúngicas/mortalidad , Enfermedades Pulmonares Fúngicas/parasitología , Activación de Macrófagos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/parasitología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ratones Transgénicos , Hipersensibilidad Respiratoria/parasitologíaAsunto(s)
Ascaris/aislamiento & purificación , Heces/parasitología , Inmunoglobulina E/sangre , Hipersensibilidad Respiratoria/parasitología , Infecciones del Sistema Respiratorio/parasitología , Animales , Biomarcadores/sangre , Humanos , Inmunoglobulina E/inmunología , Pruebas de Sensibilidad Parasitaria , Hipersensibilidad Respiratoria/sangre , Infecciones del Sistema Respiratorio/sangreAsunto(s)
Humanos , Animales , Ascaris/aislamiento & purificación , Heces/parasitología , Inmunoglobulina E/sangre , Hipersensibilidad Respiratoria/parasitología , Infecciones del Sistema Respiratorio/parasitología , Biomarcadores/sangre , Inmunoglobulina E/inmunología , Pruebas de Sensibilidad Parasitaria , Hipersensibilidad Respiratoria/sangre , Infecciones del Sistema Respiratorio/sangreRESUMEN
The studies were carried out between 1997-1999 within the administrative district of Torun. Forty sports pigeon breeders together with their pigeonswere understudy annually. The collected material allowed noticing the following issues: in 1997 and 1998 the Argas reflexus (Fabricius, 1794) was present in dovecotes (individuals) and t he breeds' owners were pricked. In 1998 numerous specimens of the A. reflexus were obtained from the material from the sanitary-epidemiological station. The specimens were collected from the bodies of the people, family members and from their flat located on the highest third floor of the old house. In the mite-infected dovecotes and in the old houserooms, the following steps were suggested: mechanical cleansing, whitewashing, disinfecting, and triple disinsecting, with fourteen-day-long intervals. The people with the symptoms of acariosis were subjected to treatment with calcium, anti-allergic, and anti-fever mixtures, and, in some cases, cortisone ointments were applied. In spite of a considerable growth in the symptoms, the used methods turned out to be successful in all the studied cases.