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1.
Immunol Lett ; 255: 10-20, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36646290

RESUMEN

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.


Asunto(s)
Asma , Microbiota , Obesidad Materna , Embarazo , Femenino , Humanos , Obesidad Materna/complicaciones , Obesidad Materna/patología , Pulmón/patología , Obesidad
2.
Eur J Microbiol Immunol (Bp) ; 10(3): 165-171, 2020 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-32857712

RESUMEN

Control of canine visceral leishmaniasis (CVL), a major zoonotic disease in Brazil and many other tropical and subtropical countries, remains difficult as an accurate and reliable diagnosis is still missing. In endemic regions, infected dogs are the main parasitic reservoir host of human Visceral leishmaniasis (VL) infection. Vaccination of dogs against Leishmania infection constitutes an important strategy to prevent or to better control CVL, thus, a serological test that can discriminate between antibodies induced by immunization versus infection is highly desirable in order to improve and simplify diagnosis. Here, four recombinant proteins were evaluated for their ability to detect and differentiate between dogs that are infected with Leishmania or have been immunized with the anti-Leishmania vaccine Leish-Tec®. Receiver operating characteristic (ROC) curve analysis of the four Leishmania-specific IgG ELISA revealed superior performance of rK28, followed by rKLO8, rK39 and rLb6H. The rK28-based ELISA revealed not only the best accuracy against CVL, but also the lowest cross-reactivity with sera from Leish-Tec® immunized dogs. Our data show that the rK28-based ELISA is highly suitable for CVL screening as it shows high sensitivity with simultaneous low cross-reactivity. Further, the high specificity of the rKLO8 indicates its suitability for the confirmation of CVL diagnosis.

3.
Int Immunopharmacol ; 83: 106422, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32251959

RESUMEN

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.


Asunto(s)
Cromolin Sódico/farmacología , Esofagitis Eosinofílica/inmunología , Estabilizadores de Mastocitos/farmacología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/inmunología , Médula Ósea/patología , Modelos Animales de Enfermedad , Esofagitis Eosinofílica/inducido químicamente , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/patología , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/inmunología , Mucosa Esofágica/patología , Fibrosis/inmunología , Fibrosis/patología , Inmunidad/efectos de los fármacos , Inmunidad/inmunología , Tejido Linfoide/efectos de los fármacos , Tejido Linfoide/inmunología , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/toxicidad
4.
Mem Inst Oswaldo Cruz ; 113(5): e170467, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29513821

RESUMEN

BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lepra Multibacilar/diagnóstico , Lepra Paucibacilar/diagnóstico , Estudios de Casos y Controles , Trazado de Contacto , Ensayo de Inmunoadsorción Enzimática , Humanos , Lepra Multibacilar/inmunología , Lepra Paucibacilar/inmunología , Mycobacterium leprae/inmunología , Curva ROC , Sensibilidad y Especificidad
5.
Mem. Inst. Oswaldo Cruz ; 113(5): e170467, 2018. tab, graf
Artículo en Inglés | LILACS | ID: biblio-894925

RESUMEN

BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.


Asunto(s)
Inmunoglobulina G/sangre , Lepra Multibacilar/diagnóstico , Lepra Paucibacilar/diagnóstico , Mycobacterium leprae/inmunología , Curva ROC , Sensibilidad y Especificidad
6.
HU rev ; 44(3): 325-331, 2018.
Artículo en Portugués | LILACS | ID: biblio-1048091

RESUMEN

Introdução: Diversos fatores podem interferir no desenvolvimento da hanseníase, entre eles fatores genéticos, convívio com o caso de hanseníase e classificação operacional do caso. Testes sorológicos que avaliam a reatividade de anticorpos IgM e IgG frente a antígenos específicos para o Mycobacterium leprae (M. leprae) podem atuar como auxiliares na vigilância dos contatos e/ou população de risco. Objetivo: Analisar o comportamento dos testes sorológicos anti-PGL-1 sintético (NDO-HSA), anti-LID-1 e anti-NDO-LID em área não endêmica de hanseníase e sua relação com características do caso de hanseníase. Material e métodos: Trata-se de um estudo transversal, do tipo analítico, realizado com 35 contatos domiciliares (CD) dos casos de hanseníase. A coleta de dados ocorreu no período de agosto/2016 a fevereiro/2017 por meio de visitas domiciliares. A reatividade de anticorpos IgM e IgG frente aos antígenos Natural disaccharide linked to human serum albumin via octyl (NDO-HSA), Leprosy IDRI diagnostic 1 (LID-1) e Natural disaccharideoctyl - Leprosy IDRI Diagnostic 1(NDO-LID) foi avaliada por ensaio imunoenzimático (ELISA). Os dados foram exportados e analisados no software StatisticalPackage for the Social Sciences (SPSS®) 24 for Windows. Resultados: Foi observada maior proporção de positividade aos testes em CD de casos multibacilares (MB), que residiam com o caso de hanseníase na época do diagnóstico e que tinham parentesco consanguíneo com o caso. Esses casos de hanseníase MB também apresentaram soropositividade frente aos antígenos testados. O valor do índice ELISA foi maior no grupo de CD de casos MB. Houve concordância moderada e significativa (K= 0,53; p< 0,0001) entre os testes anti-NDO-HSA e anti-NDO-LID, mas não foi detectada diferença entre os testes anti-NDO-HSA e anti-LID-1 (K= -0,05; p= 0,678). A correlação foi positiva entre os três antígenos, porém, entre LID-1 e NDO-HSA, não houve significância estatística (p<0,186). Conclusão: Os resultados sugerem que testes sorológicos em conjunto com as características avaliadas nos contatos domiciliares em área não endêmica de hanseníase,podem atuar como auxiliares na detecção de indivíduos infectados pelo M. leprae, contribuindo para vigilância dos contatos domiciliares


Introduction: Several factors may interfere in the development of leprosy, including genetic factors, conviviality with leprosy patients and operational classification of the case. Serological tests performed to evaluate the reactivity of IgM and IgG antibodies response against Mycobacterium leprae (M. leprae) specific antigens may be used as auxiliary tools for transmission surveillance and/or population at risk. Objective: To analyze the performance of anti-PGL-1 (NDO-HSA), anti-LID-1 and anti-NDO-LID serological tests in non-endemic area of leprosy and the relationship with characteristics of the leprosy case. Material and methods: This is a cross-sectional analytical study of 35 household contacts (HC) of leprosy cases. Data collection was carried out from August 2016 to February 2017 with home visits. The reactivity of IgM and IgG antibodies to Natural disaccharide linked to human serum albumin via octyl (NDO-HSA), Leprosy IDRI diagnostic 1 (LID-1) and Natural disaccharide octyl - Leprosy IDRI Diagnostic 1 (NDO-LID) was evaluated through enzyme-linked immunosorbent assay (ELISA). Data were exported and analyzed using Statistical Package for Social Sciences (SPSS®) 24 for Windows. Results: A higher proportion of positivity was observed in the HC tests of multibacillary (MB) leprosy cases who lived in the same dwelling with a leprosy case at the time of diagnosis and had a degree of kinship with the case. These multibacillary leprosy cases also showed seropositivity to the antigens tests. ELISA test index value was higher in the HC group of MB leprosy cases. There was moderate agreement (K = 0.53, p <0.0001) between anti-NDO-HSA and anti-NDO-LID tests, but no difference was found between anti-NDO-HSA and anti-LID -1 (K = -0.05, p = 0.678). Three antigens were positively correlated, but there was no statistical significance (p <0.186) between LID-1 and NDO-HSA. Conclusion: The results suggest that serological tests in combination with the characteristics assessed during household contacts in a non-endemic area may represent efficient auxiliary tools for the detection of M. leprae-infected individuals, providing a contribution to the surveillance of household contacts


Asunto(s)
Pruebas Serológicas , Lepra , Ensayo de Inmunoadsorción Enzimática , Estudios Seroepidemiológicos , Factores de Riesgo , Técnicas para Inmunoenzimas , Lepra Multibacilar , Lepra/prevención & control
7.
An Acad Bras Cienc ; 89(3 Suppl): 2053-2073, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28813096

RESUMEN

This study aimed to further investigate the cytotoxicity against tumor cell lines and several bacterial strains of Annona squamosa and its mode of action. Methanol extracts of A. squamosa leaves (ASL) and seeds (ASS) were used. ASL showed significant antibacterial activity against S. aureus, K. pneumoniae and E. faecalis with MIC values of 78, 78 and 39 µg/mL respectively. Moreover, ASL exhibited significant biofilm disruption, rapid time dependent kinetics of bacterial killing, increased membrane permeability and significantly reduced the cell numbers and viability. Regarding the cytotoxicity against tumor cell lines, ASS was more active against Jurkat and MCF-7 cells, with CI50 1.1 and 2.1 µg/mL, respectively. ASL showed promising activity against Jurkat and HL60, with CI50 4.2 and 6.4 µg/mL, respectively. Both extracts showed lower activity against VERO cells and reduced the clonogenic survival at higher concentrations (IC90) to MCF-7 and HCT-116 lineages. The alkaloids anonaine, asimilobine, corypalmine, liriodenine nornuciferine and reticuline were identified in extracts by UPLC-ESI-MS/MS analysis. This study reinforced that A. squamosa presents a remarkable phytomedicinal potential and revealed that its antimicrobial mechanism of action is related to bacterial membrane destabilization.


Asunto(s)
Annona/química , Antibacterianos/farmacología , Enterococcus faecalis/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Extractos Vegetales/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Línea Celular Tumoral/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Chlorocebus aethiops , Humanos , Pruebas de Sensibilidad Microbiana
8.
An. acad. bras. ciênc ; 89(3,supl): 2053-2073, 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-886784

RESUMEN

ABSTRACT This study aimed to further investigate the cytotoxicity against tumor cell lines and several bacterial strains of Annona squamosa and its mode of action. Methanol extracts of A. squamosa leaves (ASL) and seeds (ASS) were used. ASL showed significant antibacterial activity against S. aureus, K. pneumoniae and E. faecalis with MIC values of 78, 78 and 39 µg/mL respectively. Moreover, ASL exhibited significant biofilm disruption, rapid time dependent kinetics of bacterial killing, increased membrane permeability and significantly reduced the cell numbers and viability. Regarding the cytotoxicity against tumor cell lines, ASS was more active against Jurkat and MCF-7 cells, with CI50 1.1 and 2.1 µg/mL, respectively. ASL showed promising activity against Jurkat and HL60, with CI50 4.2 and 6.4 µg/mL, respectively. Both extracts showed lower activity against VERO cells and reduced the clonogenic survival at higher concentrations (IC90) to MCF-7 and HCT-116 lineages. The alkaloids anonaine, asimilobine, corypalmine, liriodenine nornuciferine and reticuline were identified in extracts by UPLC-ESI-MS/MS analysis. This study reinforced that A. squamosa presents a remarkable phytomedicinal potential and revealed that its antimicrobial mechanism of action is related to bacterial membrane destabilization.


Asunto(s)
Humanos , Animales , Staphylococcus aureus/efectos de los fármacos , Extractos Vegetales/farmacología , Enterococcus faecalis/efectos de los fármacos , Annona/química , Klebsiella pneumoniae/efectos de los fármacos , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Membrana Celular/efectos de los fármacos , Chlorocebus aethiops , Línea Celular Tumoral/efectos de los fármacos
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