RESUMEN
CONTEXT: Ferroptosis is a novel form of cell death characterised by iron overload and lipid peroxidation. It is closely associated with many diseases, including cardiovascular diseases, tumours, and neurological diseases. The use of natural chemicals to modulate ferroptosis is of great concern because of the critical role ferroptosis plays in disease. The main active ingredient in green tea is epigallocatechin gallate (EGCG), which is the most abundant catechin in green tea. EGCG shows a wide range of biological and therapeutic effects in various diseases, including anti-inflammatory, antioxidant, anticancer, and cardioprotective. OBJECTIVE: The purpose of this article is to summarise the existing information on the relationship between EGCG and ferroptosis. METHODS: Articles related to EGCG and ferroptosis were searched in PubMed and Web of Science databases, and the literature was analysed. RESULTS AND CONCLUSION: EGCG could improve ferroptosis-related diseases and affect the development of ferroptosis by regulating the nuclear factor erythroid 2-related factor 2, autophagy, microRNA, signal transducer and activator of transcription 1, and protein kinase D1 signalling pathways.
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Type 1 diabetes mellitus is a chronic disease caused by the destruction of pancreatic beta cells. Based on the hygiene hypothesis, a growing body of evidence suggests a negative association between parasitic infections and diabetes in humans and animal models. The mechanism of parasite-mediated prevention of type 1 diabetes mellitus may be related to the adaptive and innate immune systems. Macrophage polarization is a new paradigm for the treatment of type 1 diabetes mellitus, and different host macrophage subsets play various roles during parasite infection. Proinflammatory cytokines are released by M1 macrophages, which are important in the development of type 1 diabetes mellitus. Parasite-activated M2 macrophages prevent the development of type 1 diabetes mellitus and can influence the development of adaptive immune responses through several mechanisms, including Th2 cells and regulatory T cells. Here, we review the role and mechanism of macrophage polarization in parasitic protection against type 1 diabetes mellitus.
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Diabetes Mellitus Tipo 1 , Parásitos , Enfermedades Parasitarias , Humanos , Animales , Diabetes Mellitus Tipo 1/prevención & control , Macrófagos , Citocinas , Células Th2 , Activación de MacrófagosRESUMEN
The study of immune regulation mechanisms induced by parasites may help develop new treatment methods for inflammatory diseases including type 1 diabetes, which is related to type 1 immune responses. The negative correlation between schistosomiasis infection and type 1 diabetes has been confirmed, and the mechanism of Schistosoma-mediated prevention of type 1 diabetes may be related to the adaptive and innate immune systems. Schistosoma-related molecules affect immune cell composition and macrophage polarization and stimulate an increase in natural killer T cells. Furthermore, Schistosoma-related molecules can regulate the adaptive immune responses related to the prevention of type 1 diabetes and change the Th1/Th2 and Th17/Treg axis. Our previous review showed the role of regulatory T cells in the protective of type 1 diabetes mediated by Schistosoma. Here, we aim to review the other mechanisms of schistosomiasis infection and Schistosoma-related products in regulating the immune response associated with the treatment of type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Esquistosomiasis , Animales , Diabetes Mellitus Tipo 1/prevención & control , Schistosoma , Linfocitos T Reguladores , Antígenos Helmínticos , CitocinasRESUMEN
OBJECTIVES: Malnutrition is a serious complication frequently observed in dialysis patients. Therefore, nutrition status evaluation and the early identification of malnutrition are clinically important. Trimethylamine N-oxide (TMAO) is reportedly associated with deteriorating metabolic profiles and cardiovascular diseases. The aim of our study was to investigate correlations between circulating TMAO levels and malnutrition and the risk of major adverse cardiovascular events in patients on maintenance hemodialysis. METHODS: This retrospective observational study involved 228 subjects. Fasting plasma TMAO levels were detected using liquid chromatography-tandem mass spectrometry. RESULTS: TMAO levels were significantly elevated in patients with malnutrition (8728.78 ± 704.12 ng/mL) when compared with those without (6532.1 ± 570.41 ng/mL, P < .01). TMAO levels were positively correlated with Subjective Global Assessment scores (ρ = 0.56, P = .02) and were independent risk factors for malnutrition after adjustment for multiple traditional risk factors (odds ratio = 2.07, 95% confidence interval: 1.41-3.62, P < .01). Furthermore, TMAO levels were good predictors of major adverse cardiovascular events in a 2-year follow-up period (area under the curve = 0.68, P < .01) and accuracy was increased to 74% when TMAO levels were combined with Subjective Global Assessment scores (area under the curve = 0.74, P = .02). CONCLUSIONS: Elevated TMAO levels were independently associated with a risk of malnutrition and cardiovascular disease, and could be a useful predictive biomarker for risk stratification and cardiovascular disease management for patients on dialysis.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Desnutrición , Humanos , Enfermedades Cardiovasculares/epidemiología , Diálisis Renal , Desnutrición/epidemiología , ÓxidosRESUMEN
Moxidectin (MXD) is an antiparasitic drug used extensively in veterinary clinics. In this study, to develop a new formulation of MXD, a thermosensitive gel of MXD (MXD-TG) was prepared based on poloxamer 407/188. Furthermore, the gelation temperature, the stability, in vitro release kinetics and in vivo pharmacokinetics of MXD-TG were evaluated. The results showed that the gelation temperature was approximately 27 °C. MXD-TG was physically stable and can be released continuously for more than 96 h in vitro. The Korsmeyer−Peppas model provided the best fit to the release kinetics, and the release mechanism followed a diffusive erosion style. MXD-TG was released persistently for over 70 days in sheep. Part of pharmacokinetic parameters had a difference in female and male sheep (p < 0.05). It was concluded that MXD-TG had a good stability, and its release followed the characteristics of a diffusive erosion style in vitro and a sustained release pattern in vivo.
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Macrólidos , Poloxámero , Animales , Antiparasitarios , Femenino , Macrólidos/farmacocinética , Masculino , Ovinos , TemperaturaRESUMEN
This study aimed to explore the effect and mechanism underlying the role of the Schistosoma japonicum antigen of fatty acid-binding protein (SjFABP) on the growth of the schistosomula. SjFABP levels were evaluated by quantitative real-time polymerase chain reaction of samples of mice infected with S. japonicum; SjFABP was expressed and its levels gradually increased during all stages of S. japonicum schistosomula, including on 3, 10, 14, and 21 days of the growth process. Immunohistochemistry results demonstrated that SjFABP was distributed in the parenchyma, especially in the digestive tract of the S. japonicum schistosomula. RNA interference resulted in more than 60% knockdown of SjFABP leading to a reduction in length, volume, width, and area of the schistosomula as compared to control samples, as determined by light microscopy. Terminal deoxynucleotidyl transferase dUTP nick-end labeling detection further suggested that SjFABP knockdown resulted in increased apoptosis of schistosomes. Taken together, these results suggest that SjFABP may be related to the growth and survival of S. japonicum schistosomula, thereby representing a potential target for the treatment of schistosomiasis.
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Schistosoma japonicum , Esquistosomiasis Japónica , Esquistosomiasis , Animales , Anticuerpos Antihelmínticos , Proteínas de Unión a Ácidos Grasos/genética , Etiquetado Corte-Fin in Situ , Ratones , Schistosoma japonicum/genéticaRESUMEN
In western societies, the prevalence of type 2 diabetes (T2D) is related to the hygiene hypothesis, which implies that reduced exposure to infectious factors results in a loss of the immune stimulation necessary to form the immune system during development. In fact, it has been reported that parasites, such as Schistosoma, can improve or prevent the development of T2D, which may be related to the activity of immune cells, including regulatory T cells (Tregs). Hence, Schistosoma, Tregs, and T2D share a close relationship. Schistosoma infection and the molecules released can lead to an increase in Tregs, which play an important role in the suppression of T2D. In this review, we provide an overview of the role of Tregs in the response to Schistosoma infection and the protective mechanism of Schistosoma-related molecular products against T2D.
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Diabetes Mellitus Tipo 2 , Linfocitos T Reguladores , Animales , Diabetes Mellitus Tipo 2/prevención & control , SchistosomaRESUMEN
The Schistosoma japonicum fatty acid-binding protein (FABP) is used in the cell membrane to absorb and transport fatty acids, which cannot be resynthesized by the organism and combined with hydrophobic ligands. Among the 5 stages of the worm life cycle examined, FABP messenger ribonucleic acid (mRNA) expression was highest in male adult worms, followed by the liver-stage schistosome, and was the lowest in the lung-stage schistosome. The fabp gene-coding region was cloned and expressed to obtain recombinant S. japonicum FABP (rSjFABP) with a molecular weight of approximately 18 kDa. Mice were then immunized against rSjFABP to prepare anti-FABP serum. Using immunohistochemical techniques, FABP protein was found to localize to the eggshell, parenchyma, and digestive tract. Double-stranded RNA-mediated knockdown of FABP mRNA by RNA interference decreased the number of transcripts by >70%. Moreover, the egg production rate decreased, whereas the abnormal egg ratio was significantly increased in the FABP-silenced group compared with the negative control group (P < 0.05). These results demonstrate that FABP localizes in adults and in various stages. FABP contributes to the egg-laying capacity of adults, which may be related to the reproductive function of S. japonicum.
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Proteínas de Unión a Ácidos Grasos/fisiología , Proteínas del Helminto/fisiología , Schistosoma japonicum/fisiología , Animales , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/inmunología , Proteínas de Unión a Ácidos Grasos/aislamiento & purificación , Femenino , Regulación de la Expresión Génica , Proteínas del Helminto/genética , Proteínas del Helminto/inmunología , Proteínas del Helminto/aislamiento & purificación , Inmunohistoquímica , Hígado/parasitología , Pulmón/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Schistosoma japonicum/química , Schistosoma japonicum/genéticaRESUMEN
We investigated the effect of Schistosoma japonicum adenylate kinase 1 (Sjak1) on the growth and development of schistosomula. Quantitative real-time PCR showed that Sjak1 mRNA was expressed in 3-, 10-, 14-, 18-, and 21-day-old schistosomula, and its levels increased gradually with the development of S. japonicum. Using immunohistochemical techniques, ak1 protein was found to be mainly distributed in the tegument and some parenchymal tissues of the schistosomula. Double-stranded RNA-mediated knockdowns of ak1 decreased ak1 mRNA transcripts by more than 90%, and western blot results showed that expression of ak1 protein was decreased by 66%. Scanning electron microscopy following the RNA-mediated ak1 knockdown showed that the sensory papillae did not develop. Transmission electron microscopy showed a lower mean thickness of the tegument in the Sjak1 interference group than in the negative control group. Terminal deoxynucleotidyl transferase dUTP nick-end labeling suggested higher apoptosis in the interference group than the negative control group. These results showed that ak1 may be involved in the growth and development of S. japonicum schistosomula and especially in the development of the integument. Consequently, ak1 may be a potential target in developing prevention methods for schistosomiasis in the future.
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Adenilato Quinasa/metabolismo , Schistosoma japonicum/enzimología , Schistosoma japonicum/crecimiento & desarrollo , Adenilato Quinasa/análisis , Adenilato Quinasa/genética , Animales , Apoptosis , Western Blotting , ADN/fisiología , Femenino , Regulación Enzimológica de la Expresión Génica , Técnicas de Silenciamiento del Gen/métodos , Silenciador del Gen , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Hígado/parasitología , Ratones , Ratones Endogámicos ICR , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Interferencia de ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Conejos , Reacción en Cadena en Tiempo Real de la Polimerasa , Schistosoma japonicum/genética , Schistosoma japonicum/ultraestructura , Caracoles/parasitologíaRESUMEN
Type 2 diabetes mellitus (T2D) is a prevalent inflammation-related disease characterized by insulin resistance and elevated blood glucose levels. The high incidence rate of T2D in Western societies may be due to environmental conditions, including reduced worm exposure. In human and animal models, some helminths, such as Schistosoma, Nippostrongylus, Strongyloides, and Heligmosomoides, and their products reportedly ameliorate or prevent T2D progression. T2D induces adaptive immune pathways involved in the inhibition of type 1 immune responses, promotion of type 2 immune responses, and expansion of regulatory T cells and innate immune cells, such as macrophages, eosinophils, and group 2 innate lymphoid cells. Among immune cells expanded in T2DM, type 2 immune cells and macrophages are the most important and may have synergistic effects. The stimulation of host immunity by helminth infections also promotes interactions between the innate and adaptive immune systems. In this paper, we provide a comprehensive review of intestinal helminths' protective effects against T2D.
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Inmunidad Adaptativa , Diabetes Mellitus Tipo 2/complicaciones , Helmintiasis/complicaciones , Helmintos/fisiología , Inmunidad Innata , Animales , Helmintiasis/inmunología , HumanosRESUMEN
Programmed cell death protein 10 (PCDP10) is widely distributed in animal tissues and exerts extensive biological effects. This study aimed to investigate the effect of Schistosoma japonicum PCDP10 (SjPCDP10) on the fecundity of schistosomes. We performed real-time PCR to assess Sjpcdp10 expression levels at different developmental stages of S. japonicum. Immunoprotection against S. japonicum was assessed in vivo in mice, and Sjpcdp10 expression was inhibited via RNA interference (RNAi) to determine its role in fecundity. Real-time PCR analysis revealed that Sjpcdp10 mRNA was expressed during different developmental stages in S. japonicum, reaching maximum and minimum levels in female worms and lung-stage schistosomula, respectively. Recombinant SjPCDP10 had a molecular weight of approximately 28 kDa, displaying good immunogenicity but poor immunoprotection. SjPCDP10 was primarily localized in the egg, eggshell, epiphragm of adult worms, and especially the vitelline glands of female worms. RNAi-mediated knockdown of Sjpcdp10 by greater than 90%, and the protein expression decreased by 73%, reduced the number of eggs per female worm significantly more than RNAi-mediated knockdown of Egfp (negative control) (P < 0.05). The present results indicate that Sjpcdp10 knockdown affects the fecundity of schistosomes and may play a vital role in oogenesis.
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Proteínas Reguladoras de la Apoptosis/genética , Fertilidad/genética , Proteínas del Helminto/genética , Schistosoma japonicum/inmunología , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Femenino , Proteínas Fluorescentes Verdes/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Interferencia de ARN , ARN Mensajero , ARN Interferente Pequeño/genética , Conejos , Reacción en Cadena en Tiempo Real de la Polimerasa , Schistosoma japonicum/genética , Schistosoma japonicum/parasitologíaAsunto(s)
Antígeno CTLA-4/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Interleucina-6/metabolismo , Neoplasias Pulmonares/diagnóstico , MicroARNs/metabolismo , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Línea Celular Tumoral , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a candidate subunit vaccine that induces protective immunity and elicits partial resistance to Schistosoma japonicum upon mouse and livestock vaccination. This study aimed to evaluate the effect of regulatory T cells (Tregs), which were defined as CD4+CD25+Foxp3+ cells, on the efficacy of a GAPDH vaccine against S. japonicum. BALB/c female mice were randomly divided into five groups as follows: normal, infected control, anti-CD25 monoclonal antibody (anti-CD25 mAb), GAPDH group, and co-treated with anti-CD25 mAb and GAPDH group. The worm reduction and liver egg reduction rates in the GAPDH group were 32.46% and 35.43%, respectively, which increased to 60.09% and 58.78%, respectively, after anti-CD25 mAb administration. Compared with those in the infected control group, the percentage of Tregs in the spleen decreased significantly when GAPDH and anti-CD25 mAb were used either alone or in combination. Furthermore, secretions associated with the Th1 response increased in splenocytes of the anti-CD25 mAb group, whereas the Th1 and Th2 responses increased in splenocytes of the GAPDH and co-treated groups. Compared to that in the infected control group, granuloma diameter in the GAPDH and co-treated groups increased slightly, but there were no significant differences among the groups. Our results indicate that the protective effect of the GAPDH vaccines can be improved by decreasing Tregs and enhancing the Th1- and Th2-type immune responses. Therefore, anti-CD25 mAb and GAPDH might exert synergistic effects to clear parasites by decreasing the frequency of Tregs and increasing the Th1- and Th2-type immune responses.
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Gliceraldehído-3-Fosfato Deshidrogenasas/inmunología , Schistosoma japonicum/inmunología , Linfocitos T Reguladores/inmunología , Vacunas/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Citocinas/inmunología , Femenino , Granuloma/patología , Subunidad alfa del Receptor de Interleucina-2/inmunología , Hígado/inmunología , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Esquistosomiasis Japónica/parasitología , Esquistosomiasis Japónica/prevención & control , Linfocitos T Reguladores/efectos de los fármacosRESUMEN
Type 2 diabetes is a metabolic disorder characterized by persistently elevated glucose levels. There is no effective treatment strategy for this condition, and it poses a massive economic burden globally. Schistosoma soluble egg antigen (SEA)-induced immunomodulatory mechanisms have been reported in the treatment of autoimmune disease. This study aimed to determine the ability of Schistosoma japonicum SEA to protect against type 2 diabetes in Lepr db/db mice and understand the associated mechanisms. The mice were divided into four groups: C57BL/6 (the normal group), SEA (C57BL/6 mice treated with SEA), Lepr db/db , and SEA and Lepr db/db co-treatment groups. The mice in the SEA and co-treatment groups were injected with 50 µg of SEA (twice a week for 6 weeks), and the same volume of PBS was used as control. Blood glucose, insulin, and HOMA-IR levels were measured in all mice, which were sacrificed 6 weeks after the last SEA administration. Flow cytometry was used to detect the percentages of regulatory T cells in splenocytes. ELISA was used to detect the levels of IFN-γ, IL-2, IL-4, and IL-5 in cell culture supernatants. Compared with the mice in the Lepr db/db group, the mice in the SEA + Lepr db/db group exhibited significantly reduced insulin resistance, as evidenced by the enhancement of wound healing. The frequency of spleen regulatory T cells increased significantly after SEA administration; meanwhile, the secretion of IL-4 and IL-5 in spleen cells was elevated. These results indicate that SEA can reduce insulin resistance and provide new targets for the treatment of type 2 diabetes. The potential mechanisms might be associated with increases in regulatory T cells and Th2 cytokines in Lepr db/db mice, which warrants further investigation.
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Antígenos Helmínticos , Citocinas/inmunología , Diabetes Mellitus Tipo 2/prevención & control , Óvulo/química , Schistosoma japonicum/química , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Animales , Antígenos Helmínticos/química , Antígenos Helmínticos/inmunología , Antígenos Helmínticos/farmacología , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/patología , Ratones , Óvulo/inmunología , Schistosoma japonicum/inmunología , Linfocitos T Reguladores/patología , Células Th2/patologíaRESUMEN
Schistosomiasis is a devastating disease caused by Schistosoma infection. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has emerged as a candidate vaccine component against Schistosoma japonicum, but only confers partial protection. Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates T cell activation and shows negative effects on vaccine-induced immune protection; however, its potential influence on the protective effects of a GAPDH vaccine against S. japonicum and the underlying mechanism remain unclear. In this study, we established a mouse model of S. japonicum infection, and the mice were randomly divided into uninfected, infected control, anti-CTLA-4 monoclonal antibody (anti-CTLA-4 mAb), GAPDH, and GAPDH combined with anti-CTLA-4 mAb groups to compare the protective effects against infection and the consequent tissue damage. The worm reduction rate in the GAPDH-treated infected mice was 26.58%, which increased to 54.61% when combined with anti-CTLA-4 mAb. The frequency of regulatory T cells (Tregs) was significantly higher in the anti-CTLA-4 mAb group and was lower in the GAPDH group. However, both anti-CTLA-4 mAb and GAPDH elevated the levels of the cytokines IFN-γ, IL-2, IL-4, and IL-5 in the spleens of infected mice, and their combination further enhanced cytokine production. The diameter of egg granuloma in the anti-CTLA-4 mAb group and combined treatment group increased significantly compared to that of the other groups. These results suggest that anti-CTLA-4 mAb can be used as an adjuvant to enhance the immune protection of the GAPDH vaccine via inducing the Th1 immune response, although this comes at the cost of enhanced body injury.
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Antígenos Helmínticos/inmunología , Antígeno CTLA-4/inmunología , Gliceraldehído-3-Fosfato Deshidrogenasas/inmunología , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/inmunología , Vacunas/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Esquistosomiasis Japónica/parasitología , Esquistosomiasis Japónica/prevención & control , Bazo/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
AIMS: The aim of this study was to evaluate the effect of anti-CTLA-4 monoclonal antibody (mAb) on 26-kDa glutathione-S-transferase (GST) vaccine-induced immunity against Schistosoma japonicum infection. METHODS AND RESULTS: Mice immunized with GST before infection with S japonicum cercariae were injected with anti-CTLA-4 mAb. Worm reduction rate of GST was increased from 25.41% in mice with GST immunization to 52.48% in mice with GST plus anti-CTLA-4 mAb. The percentages of regulatory T cells (Tregs) were significantly higher following administration of both GST and anti-CTLA-4 mAb, or anti-CTLA-4 mAb alone. Elevated levels of IFN-γ, IL-2, IL-4 and IL-5 were observed. CONCLUSION: These results demonstrated that CTLA-4 may inhibit the protective effect of GST vaccine, and anti-CTLA-4 mAb may be used as an adjuvant to enhance the immune protection conferred by the GST vaccine by enhancing Th1- and Th2-type immune response.
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Anticuerpos Monoclonales/inmunología , Antígeno CTLA-4/inmunología , Glutatión Transferasa/inmunología , Schistosoma japonicum/enzimología , Esquistosomiasis Japónica/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Animales , Anticuerpos Monoclonales/administración & dosificación , Femenino , Glutatión Transferasa/administración & dosificación , Glutatión Transferasa/genética , Humanos , Inmunización , Interleucina-2/genética , Interleucina-2/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Ratones , Ratones Endogámicos BALB C , Schistosoma japonicum/genética , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/inmunología , Esquistosomiasis Japónica/parasitología , Linfocitos T Reguladores/inmunología , Vacunas/administración & dosificación , Vacunas/genética , Vacunas/inmunologíaRESUMEN
The present study evaluated the impact of blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4) activity on the protective effect elicited by the fatty acid binding protein (FABP) vaccine against Schistosoma japonicum infection. Mice were randomly divided into uninfected, infected control, anti-CTLA-4 monoclonal antibody (anti-CTLA-4 mAb), FABP, and combination (anti-CTLA-4 mAb and FABP) groups. An assessment of the S. japonicum worm and egg burden in the infected mice revealed that the worm reduction-rate induced by FABP administration was increased from 26.58 to 54.61% by co-administration of the monoclonal anti-CTLA antibody (anti-CTLA-4 mAb). Furthermore, the regulatory T cell (Treg) percentage was significantly increased in mice after administration of the anti-CTLA-4 mAb, but not the FABP vaccine, and elevated levels of the cytokines interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-5 were observed in infected mice that were administered the anti-CTLA-4 mAb. Notably, the diameter of egg granulomas in the anti-CTLA-4 mAb and combination groups was significantly increased compared to that observed in the infected control group. Together, these results suggest that co-administering the FABP vaccine and anti-CTLA-4 treatment may have synergistically increased the immunoprotective effect of the FABP vaccine by promoting T-helper 1-type immune responses, while incurring increased tissue damage.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígeno CTLA-4/inmunología , Proteínas de Unión a Ácidos Grasos/inmunología , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/inmunología , Vacunas/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Citocinas/inmunología , Citocinas/metabolismo , Sinergismo Farmacológico , Femenino , Interacciones Huésped-Parásitos/efectos de los fármacos , Interacciones Huésped-Parásitos/inmunología , Ratones Endogámicos BALB C , Schistosoma japonicum/efectos de los fármacos , Schistosoma japonicum/fisiología , Esquistosomiasis Japónica/parasitología , Esquistosomiasis Japónica/prevención & control , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/parasitología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células TH1/parasitología , Vacunas/administración & dosificaciónRESUMEN
The prevalence of T1D in developed societies is partly based on the hygiene hypothesis, that is, the loss of exposure to infectious agents accompanies the loss of immune stimuli shaping the immune system during development. Indeed, the components of parasites, such as Schistosoma, have been reported to ameliorate or prevent the development of T1D, which might be associated with immune cell activity especially that of regulatory T cells (Tregs). Schistosoma infection can lead to the expansion of Treg. Herein, we provide a comprehensive overview of the involvement of Tregs in the response against Schistosoma infection and the mechanism of Schistosoma-associated host protection against T1D.
Asunto(s)
Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/prevención & control , Schistosoma/inmunología , Linfocitos T Reguladores/inmunología , Animales , Diabetes Mellitus Tipo 1/metabolismo , HumanosRESUMEN
Type 1 diabetes (T1D) is an autoimmune disease in which cells of the immune system destroy pancreatic ß cells, which secrete insulin. The high prevalence of T1D in developed societies may be explained by environmental changes, including lower exposure to helminths. Indeed, infection by helminths such as Schistosoma, Filaria, and Heligmosomoides polygyrus and their by-products has been reported to ameliorate or prevent the development of T1D in human and animal models. Helminths can trigger distinct immune regulatory pathways, often involving adaptive immune cells that include T helper 2 (Th2) cells and regulatory T cells (Tregs) and innate immune cells that include dendritic cells, macrophages, and invariant natural killer T cells, which may act synergistically to induce Tregs in a Toll-like receptor-dependent manner. Cytokines such as interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-ß also play an important role in protection from T1D. Herein, we provide a comprehensive review of the effects and mechanisms underlying protection against T1D by helminths.
Asunto(s)
Diabetes Mellitus Tipo 1/prevención & control , Helmintos/inmunología , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/patología , Linfocitos T Reguladores/inmunología , Animales , Células Dendríticas/inmunología , Diabetes Mellitus Tipo 1/patología , Humanos , Interleucina-10/inmunología , Interleucina-4/inmunología , Macrófagos/inmunología , Células T Asesinas Naturales/inmunología , Células Th2/inmunología , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
Schistosomiasis is one of the most devastating parasitic diseases, making it imperative to develop efficient vaccines to control the causative flatworms called schistosomes. Regulatory T cells (Tregs) and the Th1 immune response have been implicated in the effectiveness of vaccines to control schistosomiasis, but the mechanisms underlying their effects are unclear. In this study, we evaluated the role of Tregs on the efficacy of the 14 kDa FABP (fatty acid-binding protein) vaccine against Schistosoma japonicum. BALB/c female mice were randomly divided into five groups: an uninfected group, infected control group, anti-CD25 monoclonal antibody (anti-CD25 mAb) group, FABP group, and combined anti-CD25 mAb and FABP group. Compared with FABP alone, a combined treatment with FABP and anti-CD25 mAb increased the rate of S. japonicum inhibition in mice from 30.3 to 56.08% and decreased the number of eggs per gram of liver. Compared with that of the infected control group, the percentage of Tregs in the spleen decreased significantly after single or combined treatment with FABP and anti-CD25 mAb, while it increased gradually in the anti-CD25 mAb group. Further, the secretion of Th1 cytokines, IFN-γ, and IL-2 increased in splenocytes in the anti-CD25 mAb group. Our results indicate that anti-CD25 mAb partially blocks Tregs and concomitantly enhances the Th1 type immune response, thereby enhancing the protective effect of the FABP vaccine.