RESUMO
Obesity and allergic asthma are inflammatory chronic diseases mediated by distinct immunological features, obesity presents a Th1/Th17 profile, asthma is commonly associated with Th2 response. However, when combined, they result in more severe asthma symptoms, greater frequency of exacerbation episodes, and lower therapy responsiveness. These features lead to decreased life quality, associated with higher morbidity/mortality rates. In addition, obesity prompts specific asthma phenotypes, which can be dependent on atopic status, age, and gender. In adults, obesity is associated with neutrophilic/Th17 profile, while in children, the outcome is diverse, in some cases children with obesity present aggravation of atopy, and Th2 inflammation, and in others an association with a Th1 profile, with reduced IgE levels and eosinophilia. These alterations occur due to a complex group of factors among which the microbiome has been recently explored. Particularly, evidence shows its important role in susceptibility or resistance to asthma development, via gut-lung-axis, and demonstrates its relevance to the immune pathogenesis of the syndrome. Few studies address the relevance of the lung microbiome in shaping the immune response, locally. However, specific bacteria, like Moraxella catarrhalis, Haemophilus influenza, and Streptococcus pneumoniae, correlate with important features of the obese-asthmatic phenotype. Although maternal obesity is known to increase asthma risk in offspring, the impact on lung colonization is unknown. This review details the main key immune mechanisms involved in obesity-aggravated asthma, featuring the effect of maternal obesity in the establishment of gut and lung microbiota of the offspring, acting as potential childhood asthma inducer.
Assuntos
Asma , Microbiota , Obesidade Materna , Gravidez , Feminino , Humanos , Obesidade Materna/complicações , Obesidade Materna/patologia , Pulmão/patologia , ObesidadeRESUMO
Leprosy remains endemic in several developing countries, such as India and Brazil, in part due to delayed diagnosis that facilitates ongoing transmission. Although immunoglobulins against several Mycobacterium leprae antigens have been indicated for the early diagnosis, and IgA participates in the early stages of leprosy and in subclinical infection, relatively little research has examined anti-M. leprae IgA responses. Here, we investigated serum IgA reactivity against NDO-HSA, LID-1 and NDO-LID, in paucibacillary (PB) and multibacillary (MB) patients and their household contacts, using enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy of each ELISA was evaluated by receiver operating characteristic (ROC) curve analysis. Our data reveal elevated IgA serum levels against the three M. leprae specific antigens in MB patients, whereas IgA reactivity in PB patients was increased only to NDO-HSA. Further, MB and PB household contacts displayed higher IgA reactivity to NDO-HSA than non-endemic controls. Our data suggest measurement of serum IgA against NDO-HSA as an additional tool in the diagnosis and classification of the disease, with potential utility for household contact follow-up.
RESUMO
Eosinophilic esophagitis (EoE) is an emergent chronic disease of the esophagus. The immunopathological process in EoE is characterized by Th2 immune response and prominent eosinophilic influx, in response to common food allergens. The classical treatment consists of allergen elimination diet and systemic/topical corticosteroid therapy. Nevertheless, patients do not always comply to treatment, and the prolonged corticosteroid therapy can cause side effects, therefore, there is an immediate need for new therapeutic approach for EoE. Disodium cromoglicate (DSCG) is a substance broadly used in allergic asthma treatment, and a well-known mast cell activation stabilizer. However, its effect in EoE have not been evaluated yet. This study aimed to assess the effects of DSCG treatment in an EoE experimental model. Male Balb/C mice were subcutaneously sensitized for five days with OVA, and subsequently orally OVA-challenged, DSCG administration was performed between the OVA-challenges. DSCG treatment not only reduced eosinophilic and mast cell influx, as well as reduced fibrosis. In addition, tslp, GATA3, IL-5, FoxP3 and IL-10 mRNA expression were reduced in esophageal mucosa, associated with lower Th2 (CD3+CD4+GATA3+IL4+) and B cells (CD19+CD40+) number in peripheral lymphoid organs. In conclusion, the data demonstrate DSCG treatment was effective in reducing mast cell activation and Th2 immune response, important immunopathological EoE features. Therefore, the use of DSCG as an EoE treatment can be considered a promising therapeutic approach to treat this disease.
Assuntos
Cromolina Sódica/farmacologia , Esofagite Eosinofílica/imunologia , Estabilizadores de Mastócitos/farmacologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/patologia , Modelos Animais de Doenças , Esofagite Eosinofílica/induzido quimicamente , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/patologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/imunologia , Mucosa Esofágica/patologia , Fibrose/imunologia , Fibrose/patologia , Imunidade/efeitos dos fármacos , Imunidade/imunologia , Tecido Linfoide/efeitos dos fármacos , Tecido Linfoide/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/toxicidadeRESUMO
PURPOSE: The spleen presents numerous functions, including the production of immunoglobulins and blood filtration, removing microorganisms and cellular debris. The spleen also has anatomical and functional relationship with the liver, but there are few studies on this topic. The aim of this study was to assess the effect of splenectomy and autologous spleen transplantation on both filtering functions of spleen and acetaminophen-induced hepatotoxicity. MATERIALS AND METHODS: Fifty-two BALB/c mice were randomized into four groups: splenectomized; splenectomy and splenic autotransplantation in the greater omentum; sham operated control; and non-operated control. At day 7th, 14th, and 28th after surgery, splenic filtration was assessed by counting Howell-Jolly bodies (HJB) and pitted red cells (PIT). The animals received 400 mg/kg acetaminophen by gavage at day 28th and after 12 or 24 hours were euthanized for evaluation of splenic and hepatic morphology. RESULTS: The splenectomized group demonstrated reduced filtration of HJB and PIT in all analyzes, while the autotransplanted group developed progressive recovery of function after the 14th day. At day 28 after surgery the implants showed similar histology in comparison to normal spleen. Liver histology showed more intense centrilobular necrosis in splenectomized group in comparison to the others, suggesting a protective role of spleen in acetaminophen-induced liver injury. CONCLUSIONS: Splenic implants showed structural and functional recovery, demonstrating the ability of autologous implant to rescue filtering function of intact spleen. Furthermore, the integrity of splenic function appears to influence liver morphology, since the presence of the splenic implants mitigated the effects of chemically-induced liver damage.