RESUMO
Human infection by Schistosoma mansoni affects more than 100 million people worldwide, most often in populations of developing countries of Africa, Asia, and Latin America. The transmission of S. mansoni in human populations depends on the presence of some species of Biomphalaria that act as an intermediate host. The compatibility between S. mansoni and its intermediate host is influenced by behavioral, physiological, and genetical factors of the mollusc and the parasite. The susceptibility level of the mollusc has been attributed to the capacity of internal defense system (IDS)-hemocytes and soluble components of the hemolymph-to recognize and destroy the parasite, and this will be the center of interest of this paper. The schistosome-resistant Biomphalaria can be an alternative strategy for the control of schistosomiasis.
RESUMO
Eremanthus erythropappus (DC) McLeisch, a plant popularly known as Candeia (Asteraceae), has high therapeutic potential. In this study, the in vitro schistosomicidal potentials of the ethanolic, dichloromethane and hexane extract of branches were evaluated. Couples of worms obtained from the infected mice were cultured in RPMI supplemented with foetal bovine serum and antibiotics. Four pairs of adult worms were exposed to increasing concentrations of each extract and examined by light microscope. The extracts at 100 and 200 µg mL(-1) had schistosomicidal activity, as demonstrated by the analysis of several aspects such as tegument darkening, absence of motility, incapacity of adhesion in culture plate and absence of egg in culture medium. At 50 and 75 µg mL(-1), the dichloromethane and hexane extracts were highly effective. The results suggest that these extracts could be useful in the development of new schistosomicidal drugs.
Assuntos
Asteraceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Esquistossomicidas/química , Esquistossomicidas/farmacologia , Animais , Camundongos , Schistosoma/efeitos dos fármacosRESUMO
The surface of the schistosomula is an important target for host immune system attack because the tegument represents the interface between host and parasite and thus is a potential candidate for the development of new intervention strategies. In this study, we evaluated the ability of schistosomula tegument (Smteg) to induce protection in mice. Immunization of mice with Smteg together with Freund adjuvant induced a Th1 type of immune response associated with a significant reduction in worm burden (43-48%), eggs trapped in the liver (65%), eggs eliminated in the faeces (59-60%) and granuloma number (41%). Lastly, during an in vitro study, worms from mice immunized with Smteg showed damage in the adult worm tegument and impaired egg laying.
Assuntos
Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Animais , Citocinas/biossíntese , Modelos Animais de Doenças , Fezes/parasitologia , Feminino , Adjuvante de Freund/administração & dosagem , Fígado/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Contagem de Ovos de Parasitas , Schistosoma mansoni/ultraestrutura , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologia , Células Th1/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
The use of chemotherapy on a mass scale in endemic areas may lead to the appearance of resistant isolates through the mechanism of selective drug pressure. Studies have demonstrated that praziquantel (PZQ) is able to inhibit the excretory activity and to cause tegumental damage in Schistosoma mansoni adult worms. The use of the probe resorufin to evaluate excretory activity, as well as the probe Hoechst 33258 to detect tegumental damage in adult worms, may represent a method to identify resistant (or less susceptible) isolates. The purpose of the present work was to compare the changes caused by PZQ in the function of the excretory system and in the integrity of the tegument of adult worms from the LE isolate (susceptible to PZQ) and the LE-PZQ isolate (less susceptible to PZQ). Worms from the isolate LE-PZQ showed less severe tegumental lesions, in both in vitro and in vivo experiments, detected by labelling with Hoechst 33258 and continued to have a functional excretory system as shown by labelling with resorufin in vitro.
Assuntos
Anti-Helmínticos/farmacologia , Resistência a Medicamentos , Corantes Fluorescentes , Praziquantel/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Bisbenzimidazol/metabolismo , Sistema Digestório/metabolismo , Sistema Digestório/patologia , Corantes Fluorescentes/metabolismo , Oxazinas/metabolismo , Testes de Sensibilidade Parasitária/métodos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Pele/metabolismo , Pele/patologiaRESUMO
Ageing is associated with several alterations in the immune system. Our aim in this study was to compare the development of immunity to Schistosoma mansoni infection in young versus aged C57Bl/6 mice using the liver as the main organ to evaluate pathological alterations and immune responses. In the acute phase, young mice had large liver granulomas with fibrosis and inflammatory cells. Chronic phase in young animals was associated with immunomodulation of granulomas that became reduced in size and cellular infiltrate. On the other hand, aged animals presented granulomas of smaller sizes already in the acute phase. Chronic infection in these mice was followed by no alteration in any of the inflammatory parameters in the liver. In concert with this finding, there was an increase in activated CD4+ T, CD19+ B and NK liver cells in young mice after infection whereas old mice had already higher frequencies of activated B, NK and CD4+ T liver cells and infection does not change these frequencies. After infection, liver production of inflammatory and regulatory cytokines such as IFN-gamma, IL-4 and IL-10 increased in young but not in old mice that had high levels of IL-4 and IL-10 regardless of their infection status. Our data suggest that the unspecific activation status of the immune system in aged mice impairs inflammatory as well as regulatory immune responses to S. mansoni infection in the liver, where major pathological alterations and immunity are at stage. This poor immune reactivity may have a beneficial impact on disease development.
Assuntos
Envelhecimento/imunologia , Hepatopatias/imunologia , Hepatopatias/patologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/patologia , Animais , Linfócitos B/imunologia , Separação Celular , Citocinas/biossíntese , Citocinas/imunologia , Citometria de Fluxo , Inflamação/imunologia , Inflamação/patologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/imunologiaRESUMO
Biomphalaria tenagophila of Taim strain is able to completely destroy Schistosoma mansoni sporocyst few hours after parasite penetration, although the mechanism is still not well known. In this experimental work we show that passive transference of cell-free haemolymph, especially from B. tenagophila Taim, resulted in higher resistance of B. tenagophila Cabo Frio to S. mansoni infection. This effect was demonstrated in vivo, by the reduction in the infection rate, and the significantly lower production of sporocysts and cercariae of the parasite in snails treated with Taim cell-free haemolymph compared to CBSS-inoculated snails. The protective effect of Taim cell-free haemolymph was also observed during the in vitro interaction between haemocytes and sporocysts. In this system, addition of B. tenagophila cell-free haemolymph, especially from Taim strain, was responsible for significant increase in sporocyst mortality compared to B. glabrata cell-free haemolymph or culture medium. Moreover, the combination of Taim cell-free haemolymph and Cabo Frio haemocytes increased significantly the mortality of sporocysts. The results show that Taim cell-free haemolymph would act direct and indirectly on destruction of S. mansoni sporocysts. The results also suggest that cell-free haemolymph indirectly increases parasite recognition by the circulating granulocytes and it is species specific.
Assuntos
Biomphalaria/imunologia , Biomphalaria/parasitologia , Hemolinfa/imunologia , Oocistos/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Animais , Sobrevivência Celular , Humanos , Imunização PassivaRESUMO
The review gives a detailed account of the history of drug development, treatment and drug resistance for clinical therapy of schistosomiasis mansoni, specially emphasizing the importance of Brazilian contribution on antischistosomal chemotherapy, as well as on the control of this parasitic disease.
Assuntos
Anti-Helmínticos/história , Anti-Helmínticos/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/história , Animais , Brasil/epidemiologia , Resistência a Medicamentos , História do Século XX , História do Século XXI , Humanos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/epidemiologiaRESUMO
Evolutionary and closer structural relationships are demonstrated by phylogenetic analysis, peptide prediction and molecular modelling between Solanum tuberosum apyrase, Schistosoma mansoni SmATPase 2 and Leishmania braziliensis NDPase. Specific protein domains are suggested to be potentially involved in the immune response, and also seem to be conserved during host and parasite co-evolution. Significant IgG antibody reactivity was observed in sera from patients with American cutaneous leishmaniasis (ACL) and schistosomiasis using potato apyrase as antigen in ELISA. S. mansoni adult worm or egg, L. braziliensis promastigote (Lb) and Trypanosoma cruzi epimastigote (EPI) have ATP diphosphohydrolases, and antigenic preparations of them were evaluated. In ACL patients, IgG seropositivity was about 43% and 90% for Lb and potato apyrase, respectively, while IgM was lower (40%) or IgG (100%) seropositivity for both soluble egg (SEA) and adult worm (SWAP) antigens was higher than that found for potato apyrase (IgM=10%; IgG=39%). In Chagas disease, IgG seropositivity for EPI and potato apyrase was 97% and 17%, respectively, while the IgM was low (3%) for both antigens. The study of the conserved domains from both parasite proteins and potato apyrase could lead to the development of new drug targets or molecular markers.
Assuntos
Apirase/imunologia , Sequência Conservada/imunologia , Mapeamento de Epitopos , Parasitos/enzimologia , Parasitos/imunologia , Solanum tuberosum/enzimologia , Sequência de Aminoácidos , Animais , Anticorpos Antiprotozoários/imunologia , Apirase/química , Doença de Chagas/sangue , Doença de Chagas/imunologia , Humanos , Leishmania braziliensis/enzimologia , Leishmania braziliensis/genética , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/sangue , Leishmaniose Cutânea/imunologia , Dados de Sequência Molecular , Parasitos/genética , Filogenia , Estrutura Terciária de Proteína , Schistosoma mansoni/enzimologia , Schistosoma mansoni/genética , Schistosoma mansoni/imunologia , Esquistossomose/sangue , Esquistossomose/imunologia , Alinhamento de SequênciaRESUMO
The activity of oxamniquine (OXA), praziquantel (PZQ), and a combination of both drugs was evaluated at the intramolluscan phase of Schistosoma mansoni. Biomphalaria glabrata snails infected with S. mansoni were treated with 500 mg/kg OXA, 1000 mg/kg PZQ or with 250 mg/kg OXA and 500 mg/kg PZQ, in association, at the pre-patent and patent phases of infection. The results showed that either treatments with OXA or PZQ, alone, at the pre-patent period, delayed the parasite's development, increasing the pre-patent period by approximately 10 days. At the same pre-patent period, treatment with a combination of OXA/PZQ delayed the parasite's development even more, extending the pre-patent period up to 56 days. At the patent period, treatment with OXA and PZQ, alone, interrupted cercarial shedding. When the snails were treated with 1000 mg/kg PZQ, the cercarial production was re-established 15 days after treatment, but in lower numbers than those obtained before treatment, whereas the snails treated with 500 mg/kg OXA were able to shed cercariae in similar quantities to those observed before treatment. The association 250 mg/kg OXA+500 mg/kg PZQ, at the patent period, not only discontinued cercarial shedding, but also led to the "cure" of the snails, showing a synergistic effect of this combination of drugs. These results suggest that this model will be useful for selection of resistant parasites, as well as for screening new antischistosomal drugs.
Assuntos
Anti-Helmínticos/farmacologia , Biomphalaria/parasitologia , Oxamniquine/farmacologia , Praziquantel/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/parasitologia , Animais , Quimioterapia Combinada , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/tratamento farmacológico , Estatísticas não ParamétricasRESUMO
Biomphalaria glabrata snails are major hosts for the digenetic trematoda Schistosoma mansoni, the causative agent of human schistosomiasis. The success or failure of the infection will be dependent on the mobilization of the molluskan internal defense system, where a major role will be played by circulating hemocytes produced by the APO (amebocyte-producing organ) of the snail. In this report, the primary culture of the APO region of B. glabrata was obtained for the first time, as well as a control culture of the ovotestis. Three different cell populations migrated easily from the explants in culture, with no need of any dispersion agent. The cells grew in suspension at an incubation temperature of 15 degrees C and the cultures were maintained viable for up to two weeks. Two of these cell populations obtained resembled cell types known to be present in the hemolymph of Biomphalaria. The availability of APO cells in culture may contribute to a better understanding of the internal defense in mollusks, in general, as well as the specific response of B. glabrata to S. mansoni infection.