RESUMO
A role of IL-10 is down-regulating T-cell responses to schistosome antigens. Since SmATPDases can be correlated to modulation of the immune response, we evaluated the expression of enzymes in S. mansoni eggs. Faecal samples were collected from 40 infected individuals to detect coding regions of the SmATPDases. The cytokines were measured in supernatants of PBMC. The analysis was performed by the global median determination and set up high producers (HP) of cytokines. Six individuals expressed SmATPDase1, six expressed SmATPDase2 and six expressed both enzymes. The group who expressed only SmATPDase1 showed a high frequency of IFN-γ, TNF IL-4 HP; individuals who expressed only SmATPDase2 showed a high frequency of IFN-γ, IL-6 and IL-4 HP; and individuals who expressed both enzymes showed a high frequency of IL-10 HP. The comparison of the IFN-γ/IL-10 ratio presented higher indices in the group who had SmATPDase 2 expression than those who had the expression of both enzymes. The positive correlation between infection intensity and IL-10 levels remained only in the positive SmATPDase group. The IL-10 is the only cytokine induced by the expression of both enzymes. Our data suggest that the expression of both enzymes seems to be a factor that modulates the host immune response by inducing high IL-10 production.
Assuntos
Schistosoma mansoni , Esquistossomose mansoni , Animais , Humanos , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Leucócitos Mononucleares , Citocinas/metabolismoRESUMO
We investigated the cytokine profile of peripheral mononuclear cells from chronic osteomyelitis (OST) patients following in vitro stimulation with staphylococcal enterotoxin A (SEA). We demonstrate that stimulation with SEA induced prominent lymphocyte proliferation and high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 secretion in both OST and non-infected individuals (NI). Even though stimulation with SEA had no impact on IL-6 production in either patient group, the baseline level of IL-6 production by cells from OST patients was always significantly less than that produced by cells from NI. After classifying the osteomyelitic episodes based on the time after the last reactivation event as "early" (1-4 months) or "late" osteomyelitis (5-12 months), we found that increased levels of TNF-α and IL-4 in combination with decreased levels of IL-6 were observed in the early episodes. By contrast, increased levels of IL-10, IL-2 and IL-6 were hallmarks of late episodes. Our data demonstrate that early osteomyelitic episodes are accompanied by an increased frequency of "high producers" of TNF-α and IL-4, whereas late events are characterised by increased frequencies of "high producers" of IL-10, IL-6 and IL-2. These findings demonstrate the distinct cytokine profiles in chronic osteomyelitis, with a distinct regulation of IL-6 production during early and late episodes.
Assuntos
Citocinas/biossíntese , Enterotoxinas/imunologia , Leucócitos Mononucleares/imunologia , Óxido Nítrico/biossíntese , Osteomielite/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Doença Crônica , Feminino , Humanos , Interleucinas/biossíntese , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Osteomielite/microbiologia , Fator de Necrose Tumoral alfa/biossíntese , Adulto JovemRESUMO
BACKGROUND: The Kato-Katz (KK) stool smear is the standard test for the diagnosis of Schistosoma mansoni infection, but suffers from low sensitivity when infections intensities are moderate to low. Thus, misdiagnosed individuals remain untreated and contribute to the disease transmission, thereby forestalling public health efforts to move from a modality of disease control to one of elimination. As an alternative, the urine-based diagnosis of schistosomiasis mansoni via the circulating cathodic antigen immuno-chromatographic test (CCA-ICT) has been extensively evaluated in Africa with the conclusion that it may replace the KK test in areas where prevalences are moderate or high. METHODS AND FINDINGS: The objective was to measure the performance of the CCA-ICT in a sample study population composed of residents from non-endemic and endemic areas for schistosomiasis mansoni in two municipalities of Minas Gerais state, Brazil. Volunteers (130) were classified into three infection status groups based on duplicate Kato-Katz thick smears from one stool sample (2KK test): 41 negative individuals from non-endemic areas, 41 negative individuals from endemic areas and 48 infected individuals from endemic areas. Infection status was also determined by the CCA-ICT and infection exposure by antibody ELISA (enzyme-linked immunosorbent assay) to S. mansoni soluble egg antigen (SEA) and soluble (adult) worm antigen preparation (SWAP). Sensitivity and specificity were influenced by whether the trace score visually adjudicated in the CCA-ICT was characterized as positive or negative for S. mansoni infection. An analysis of a two-graph receiver operating characteristic was performed to change the cutoff point. When the trace score was interpreted as a positive rather than as a negative result, the specificity decreased from 97.6% to 78.0% whereas sensitivity increased from 68.7% to 85.4%. A significantly positive correlation between the CCA-ICT scores and egg counts was identified (r = 0.6252, p = 0.0001). However, the CCA-ICT misdiagnosed as negative 14.6% of 2KK positive individuals, predominantly those with light infections (fewer than 100 eggs/g feces). Considering 2KK as reference test, the discriminating power of the CCA-ICT (the area under the curve [AUC] = 0.817) was greater than the SEA-ELISA (AUC = 0.744) and SWAP-ELISA (AUC = 0.704). CONCLUSION: Our data for the performance of the CCA-ICT in the Brazilian communities endemic for schistosomiasis mansoni support those from Africa, i.e., in areas with greater infection prevalence and intensities, the CCA-ICT may be useful as a tool to indicate community-based preventative chemotherapy without individual diagnosis. However, because of the Brazilian Ministry of Health's recommendation for individual diagnosis in areas where prevalence is less than 15%, i.e., those areas in which infection intensities are likely to be lowest, the CCA-ICT lacks the sensitivity to be used as standalone diagnostic tool.
Assuntos
Antígenos de Helmintos/isolamento & purificação , Cromatografia de Afinidade/métodos , Glicoproteínas/isolamento & purificação , Proteínas de Helminto/isolamento & purificação , Schistosoma mansoni , Esquistossomose mansoni/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Anti-Helmínticos , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Ensaio de Imunoadsorção Enzimática/métodos , Fezes/química , Fezes/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquistossomose mansoni/epidemiologia , Sensibilidade e Especificidade , Adulto JovemRESUMO
Os índios Maxakali pertencem a uma etnia naturalmente brasileira que aindahoje preserva vários aspectos de sua cultura. Com a inserção do europeu em terras brasileiras, além de parte de sua cultura original ter sido afetada, várias doenças foram inseridas em seu meio, levando a um índice elevado de mortandade, decorrente da pouca resistência dos nativos aos micro-organismosintroduzidos. Além disso, o quadro se agravou na medida em que as condiçõesde escravidão, maus-tratos e trabalhos forçados impostos pelos colonizadores foram se intensificando. O estudo da leishmaniose visceral nas aldeias Maxakali se justifica pelas características encontradas nessa populaçãoextremamente jovem, que favorece a instalação da leishmaniose visceral de forma mais grave. A presença de cães nas aldeias e o contato constante de indígenas com as matas são fortes indícios da ocorrência do ciclo de transmissão dessa doença. Neste estudo, objetivamos pesquisar a soropositividade de cães presentes no ambiente peridomiciliar dos Maxakali residentes nos Polos Base deÁgua Boa e Pradinho.
Assuntos
Brasil , Saúde de Populações Indígenas , Indígenas Sul-Americanos , Doenças Parasitárias , Leishmaniose VisceralRESUMO
Schistosoma mansoni infection may occur either as an acute infection in individuals who have recently visited an endemic area, with no previous contact with the parasite, or as a lasting chronic disease, if not interrupted by specific chemotherapy. The acute phase is characterized by symptoms such as fever, cough, diarrhea, anorexia, and arthralgias in combination with leukocytosis and eosinophilia, and a high cellular immune response to schistosome antigens especially those from the parasite's eggs. In the chronic phase, most patients living in endemic areas are asymptomatic, and their immune responses to egg antigens are modulated. A few develop periportal fibrosis of the liver, which may result in the hepatosplenic form of the disease. The humoral response (IgG, IgM and IgE) in acute patients to egg and worm antigens does not differ from the chronic phase. However, a high level of IgG and IgM antibodies to KLH were detected in acute patients. Acute patients express a considerably higher in vitro cellular responsiveness than do chronic patients, especially to egg antigens. They present a mixed profile of Th1 and Th2 cytokines. Ultrasound examinations of endemic population reveal a high heterogeneity between the patients as regards the presence and intensity of periportal fibrosis. Most patients are asymptomatic and their immune responses to schistosoma egg antigens (SEA) are modulated. In contrast, a high percentage of patients with incipient fibrosis (early stage of hepatosplenic) responded strongly to SEA. Patients with advanced hepatosplenic disease were likely to be non-responders to SEA. Most of the chronic patients presented a Th2 profile with low production of interferon-gamma (IFN-gamma). The intensity of infection favors the production of interleukin (IL)-10. After adjusting for age, sex, and intensity of infection, a strong correlation was observed between the production of IL-13 and the degree of fibrosis. Chronic asymptomatic patients and those with incipient fibrosis expressed very high levels of heterogeneity of their antibody responses. IgG response to soluble worm antigen preparation (SWAP) was distinct and significantly higher in hepatosplenic patients than in those asymptomatic or with incipient fibrosis. Levels of IgG4 to SEA were significantly higher in sera from patients with incipient fibrosis as compared to uninfected and hepatosplenic groups. Polyclonal idiotypic antibodies and their fragments F(ab')2, directly stimulate in culture T cells of schistosomiasis patients in presence of IL-1. Polyclonal idiotypic antibodies are able to modulate in vitro granuloma formation around SEA-polyacrylamide. The importance of idiotypes for protection or pathology in schistosomiasis is still not clear.
Assuntos
Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Adulto , Idoso , Animais , Anticorpos Anti-Helmínticos/sangue , Brasil , Citocinas/metabolismo , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Leucócitos Mononucleares/imunologia , Cirrose Hepática , Esquistossomose mansoni/patologia , Esquistossomose mansoni/fisiopatologiaRESUMO
Previous studies have demonstrated that distinct immune response profiles can be correlated with the development/maintenance of different clinical forms of human schistosomiasis. We have previously shown that individuals with the more severe clinical forms of the disease such as those presenting different levels of fibrosis or with the hepatosplenic (HS) clinical form of the disease show significantly different immune response when compared with those with the intestinal clinical form (INT). To better understand the immune mechanisms associated with the clinical form of the schistosomiasis, in this study, we present the results of the evaluation, at a single cell level, of the cytokine patterns as well as the chemokine receptors expression by T-cell subsets after in vitro short-term stimulation with soluble egg antigens as well as the ex vivo frequency analysis of putative regulatory CD4+CD25HIGH+ T-cell subset in the peripheral blood mononuclear cells. We observed an increase on IL-4+, IL-5+ and IL-10+ cells both in the CD4+ and CD8+ lymphocytes in INT and a significant decrease on the number of IL-4+, IL-5+ and IL-10+ T-lymphocytes for HS. However, patients with detectable fibrosis presented decrease on IL-10+ (both CD4+ and CD8+ lymphocytes) and basal levels of IL-4 and IL-5. These data suggested that although INT group is under the influence of an effective immunoregulated immune response, mainly due to the high percentage of IL-10+ cells, it presents a mixed type (Type1/Type-2) immune profile. Moreover, the chemokine receptors expression demonstrated that CXCR3 and CXCR4 by CD4+ T-cells in INT may dictate the selective profile of IL-10 associated with the immunomodulatory events in human schistosomiasis. Additionally, the ex vivo analysis also suggests that higher levels of CD4+CD25HIGH+ T-cells may play a role in controlling morbidity in chronic human schistosomiasis. Taken together, these data suggest a major role of IL-10-producing CXCR4+ CD4+ T-cell subset for the asymptomatic outcome of the disease.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Citocinas/imunologia , Receptores de Quimiocinas/imunologia , Esquistossomose/imunologia , Esquistossomose/patologia , Adolescente , Adulto , Idoso , Linfócitos T CD4-Positivos/química , Células Cultivadas , Criança , Feminino , Citometria de Fluxo , Humanos , Subunidade alfa de Receptor de Interleucina-2/análise , Masculino , Pessoa de Meia-IdadeRESUMO
We investigated the cytokine profile of peripheral mononuclear cells from chronic osteomyelitis (OST) patients following in vitro stimulation with staphylococcal enterotoxin A (SEA). We demonstrate that stimulation with SEA induced prominent lymphocyte proliferation and high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 secretion in both OST and non-infected individuals (NI). Even though stimulation with SEA had no impact on IL-6 production in either patient group, the baseline level of IL-6 production by cells from OST patients was always significantly less than that produced by cells from NI. After classifying the osteomyelitic episodes based on the time after the last reactivation event as "early" (1-4 months) or "late" osteomyelitis (5-12 months), we found that increased levels of TNF-α and IL-4 in combination with decreased levels of IL-6 were observed in the early episodes. By contrast, increased levels of IL-10, IL-2 and IL-6 were hallmarks of late episodes. Our data demonstrate that early osteomyelitic episodes are accompanied by an increased frequency of "high producers" of TNF-α and IL-4, whereas late events are characterised by increased frequencies of "high producers" of IL-10, IL-6 and IL-2. These findings demonstrate the distinct cytokine profiles in chronic osteomyelitis, with a distinct regulation of IL-6 production during early and late episodes.
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Citocinas/biossíntese , Enterotoxinas/imunologia , Leucócitos Mononucleares/imunologia , Óxido Nítrico/biossíntese , Osteomielite/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Estudos de Casos e Controles , Doença Crônica , Interleucinas/biossíntese , Ativação Linfocitária , Osteomielite/microbiologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The objective of the present study was to test the hypothesis that treatment of schistosomiasis mansoni with praziquantel can alter significantly the immune response of patients and generate a reversal of the level of fibrosis. Peripheral blood mononuclear cell (PBMC) samples were collected from, and abdominal ultrasound examinations conducted on, volunteers infected with Schistosoma mansoni and living in an area where the disease is endemic, both prior to and one year after treatment with praziquantel. Subjects were classified into groups according to the level of pathology (i.e., absent, incipient, moderate, or severe fibrosis). PBMCs were stimulated with schistosome soluble egg antigens (SEA), and the levels of production of the cytokines gamma interferon (IFN-gamma), tumor necrosis factor alpha, transforming growth factor beta, and interleukin-4 (IL-4), IL-10, and IL-13 were determined. The chemotherapy was effective in reducing morbidity, particularly for individuals presenting with severe fibrosis. When levels of cytokine production in posttreatment PBMC cultures stimulated by SEA were categorized as low or high, significant differences in the distribution of IL-13 levels between groups presenting with or not presenting with fibrosis were established. Comparison of pre- and posttreatment SEA-induced cytokine levels in individuals who had experienced no change in the grade of fibrosis following chemotherapy revealed that the level of IFN-gamma decreased in subjects with fibrosis whereas that of IL-10 decreased in individuals with and without fibrosis. The data suggest that chemotherapy is effective in reducing the morbidity of the disease and that the level of IL-13 may be a useful indicator of the persistence of fibrosis following treatment
RESUMO
Duzentos e vinte e três indivíduos de área endêmica de baixa morbidade para esquistossomose e nove pacientes hospitalizados com a forma hepatoesplênica foram submetidos ao exame de fezes e clínico e à ultra-sonografia do abdômen. De acordo com os resultado dos exames de fezes e do ultra-som eles foram agrupados do seguinte modo: G1 - 63 indivíduos sem ovos de Schistosoma mansoni nas fezes; G2 - 141 indivíduos apresentando ovos de Schistosoma mansoni nas fezes, sem ecogenicidade peripttal. G3 19 indivíduos com ovos de Schistosoma mansoni nas fezes e ecogenicidade peripttal entre 3-6mm.; G4 9 pacientes hepatesplênicos com ecogenicidade peripttal > 6mm. Pelo exame físico do abdômen, a hepatomegalia na linha hemiclavicular direita foi constatada em G1, G2 E G3, respectivamente, em 11,1, 12,1 e 26,3%. Nos grupos G1, G2 e G3, houve espessamento peripttal somente em esquistossomáticos (8,5%). Alterações patológicas leves em pacientes, as quais não puderam ser detectadas pelo exame clínico, foram evidenciadas no fígado pelo ultra-som e podem ser devidas à fibrose. O grau de fibrose peripttal leve foi diminuído em 57,9% dos pacientes 12 meses após tratamento da esquistossomose com oxamniquine. Na ultra-sonografia, a média da medida do lobo esquerdo do fígado dos indivíduos de G3 foi maior que a de G1 e, a de G4 maior que a de G1 e G2. O tamanho médio do baço de G4 foi significativamente maior que o dos outros grupos e o de G3 foi maior que o de G1 e G2.