RESUMO
In the murine model, it was demonstrated that pro-inflammatory cytokines and chemokines are essential to the formation and modulation of Schistosoma-induced granulomatous inflammation. However, the relationship of these immune mediators and disease severity is hard to be established in naturally infected individuals. The current study evaluates the association between plasma concentrations of MIF, sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma mansoni-infected patients with a low parasite burden. For this propose, 97 S. mansoni-infected individuals were subjected to abdominal ultrasound analysis and clinical examination. Among them, 88 had plasma concentration of immune mediators estimated by ELISA assay. Multivariate linear regression models were used to evaluate the relationship between the plasma concentration of immune mediators and the variables investigated. Although most individuals presented low parasite burden, over 30% of them showed signs of fibrosis defined by ultrasound measurements and 2 patients had a severe form of schistosomiasis. No association between parasite burden and the plasma levels of chemokine/cytokines or disease severity was observed. There was a positive association between plasma concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or with portal vein thickness that are liver fibrosis markers. In contrast, no association was found between CCL7 plasma concentrations with any of the schistosomiasis morbidity parameters evaluated. The data showed that CCL24, sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals and their concentration would be used as prognostic makers of Schistosoma-induced liver fibrosis, even in individuals with low parasite burden.
Assuntos
Quimiocina CCL24/sangue , Quimiocina CCL3/sangue , Quimiocina CCL7/sangue , Oxirredutases Intramoleculares/sangue , Cirrose Hepática/imunologia , Fatores Inibidores da Migração de Macrófagos/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Adolescente , Adulto , Idoso , Animais , Humanos , Fígado/irrigação sanguínea , Fígado/parasitologia , Fígado/patologia , Cirrose Hepática/parasitologia , Pessoa de Meia-Idade , Veia Porta/patologia , Esquistossomose mansoni/parasitologia , Adulto JovemRESUMO
Studies performed in the last 30 years demonstrated that a strain of B. tenagophila from the Taim Biological Reserve is completely resistant to Schistosoma mansoni infection. This resistance to parasite infection is a dominant characteristic during cross breeding with susceptible B. tenagophila strains. These experiments also identified a 350 bp molecular marker that is exclusive to the Taim strain and does not occur in other geographic strains of this snail species. The Taim strain (Taim/RS) of Biomphalaria tenagophila was bred on a large scale, physically marked and introduced into a stream in which previous malacological analyses had revealed the presence of only parasite-susceptible B. tenagophila. Samples of off spring captured 4, 11 and 14 months after the introduction of the Taim strain were examined, and the susceptibility of the snails to S. mansoni infection dropped from 38.626.5% to 2.1% during the 14 months after the introduction of the Taim snail strain. A significant correlation was also observed between the absence of infection and the identification of the Taim molecular marker. These results demonstrate that the genetic marker from the Taim strain was successfully introduced into the wilds nail population. In addition, a significant relationship exists between the marker and resistance to infection...
Assuntos
Humanos , Biomphalaria/crescimento & desenvolvimento , Schistosoma mansoni/crescimento & desenvolvimentoRESUMO
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
Fasciola hepatica is a parasitic helminth that predominantly infects the liver and bile ducts of cattle and causes great losses of cattle production in the southern and southeastern regions of Brazil. The generation of liver lesions and the consequent inflammatory responses are intimately related to the migration of this parasite. The CC-group of chemokines plays a crucial role in the attraction of several cell types and in the recruitment of additional macrophages to an inflammatory focus in numerous diseases. In order to evaluate the role of CCL3 in the development of F. hepatica, we compared parasitological and pathological parameters in C57Bl/6J mice that were assigned to one of two experimental groups: the first group contained CCL3-producing mice (CCL3(+/+) mice) and the other group contained mice that were genetically deficient in CCL3 production (CCL3(-/-) mice). The mortality rate in the CCL3 non-deficient group was higher than of the deficient animals. In most animals from both experimental groups, the necropsied animals contained hemorrhages in their abdominal cavities. In the genetically modified animals, the lesioned liver areas were less extensive and presented focal and sub-capsular lesions. This work demonstrates that the development of F. hepatica is not affected by the absence of CCL3.
Assuntos
Quimiocina CCL3/genética , Fasciola hepatica , Fasciolíase/imunologia , Animais , Quimiocina CCL3/metabolismo , Fezes/parasitologia , Deleção de Genes , Regulação da Expressão Gênica , Fígado/patologia , Hepatopatias/parasitologia , Hepatopatias/patologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Nematode infections are generally followed by high rates of reinfection, leading to elevated prevalence in endemic areas. Therefore, the effective control of nematode infections depends on understanding the induction and regulation of protective mechanisms. However, most experimental models for protective immune response against nematodes use high parasite exposure, not always reflecting what occurs naturally in human populations. In this study, we tested whether infecting mice with different Strongyloides venezuelensis larvae loads would affect protective responses against reinfection. Interestingly, we found that a previous infection with 10-500 larvae conferred high rate of protection against reinfection with S. venezuelensis in mice, by destroying large numbers of migrating larvae. However, low-dose priming did not abolish adult worm maturation, as detected in high-dose primed group. Results also indicated that a previous low-dose infection delayed the development of cellular infiltrate, while a high inoculum rapidly induced these inflammatory features. Cytokine production by splenocyte cultures of challenge infected mice demonstrated that low-dose priming had increased production of IL-4 and IFN-gamma, while high-dose induced IL-4 production but not IFN-gamma. Our data support the hypothesis that low-dose nematode infection does not induce a polarized type-2 immune response, allowing adult worm survival.
Assuntos
Strongyloides/imunologia , Estrongiloidíase/imunologia , Animais , Modelos Animais de Doenças , Inflamação , Interferon gama/metabolismo , Interleucina-4/metabolismo , Larva/imunologia , Leucócitos Mononucleares/imunologia , Pulmão/parasitologia , Pulmão/patologia , Masculino , Camundongos , Baço/imunologia , Strongyloides/crescimento & desenvolvimento , Estrongiloidíase/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
An estimated quarter of the world's population possesses an infection caused by gastrointestinal nematodes, which induce a Th2 type immune response. Concomitant infection of nematodes with Mycobacterium tuberculosis, which induces a predominantly Th1 type response, is very frequent in tropical and subtropical regions. This study examined immune responses of BALB/c mice infected with Strongyloides venezuelensis and then co-infected with Mycobacterium bovis. The number of worms in the intestine, eggs in feces, cytokine production in lungs and intestine and the expression of CD80, CD86, CTLA-4 and CD28 cell markers on pulmonary cells were analysed. Our results indicate that co-infected mice had an increased parasite burden, which correlates with elevated IFN-gamma and IL-10 cytokine production and decreased IL-4 and IL-13. Moreover, decreased expression of CD80 and increased expression of CTLA-4 were observed in co-infected mice. Our data point out that susceptibility to Strongyloides venezuelensis infection is increased by Mycobacterium bovis co-infection, resulting in higher parasite survival.
Assuntos
Citocinas/metabolismo , Infecções por Mycobacterium/complicações , Mycobacterium bovis , Strongyloides/patogenicidade , Estrongiloidíase/complicações , Células Th2/imunologia , Animais , Suscetibilidade a Doenças , Fezes/parasitologia , Interferon gama/metabolismo , Interleucina-10/metabolismo , Intestinos/imunologia , Intestinos/parasitologia , Pulmão/imunologia , Pulmão/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Mycobacterium/imunologia , Infecções por Mycobacterium/microbiologia , Mycobacterium bovis/imunologia , Mycobacterium bovis/patogenicidade , Contagem de Ovos de Parasitas , Ratos , Ratos Wistar , Strongyloides/classificação , Estrongiloidíase/imunologia , Estrongiloidíase/parasitologiaRESUMO
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
Bronchoalveolar lavage (BAL) is a procedure that retrieves cells and other elements from the lungs for evaluation, which helps in the diagnosis of many pulmonary diseases. The aims of this work were to perform this procedure in dogs in the acute and chronic phases of an Angiostrongylus vasorum infection for cytological analysis and to evaluate the potential of this technique as a diagnostic method for this lung-heart worm. The BAL procedure was performed through the use of an endotracheal tube on seven A. vasorum infected dogs and on five non-infected dogs lined as a control group. Sixty days post-infection (dpi) active and live larvae were retrieved from the bronchoalveolar fluid (BALF) of all infected dogs. Furthermore, in one animal it was possible to retrieve larvae in its BALF before the pre-patent period. This work reports that the A. vasorum infection resulted in an increase of relative neutrophils and eosinophils counts. In contrast, there was a significant decrease in the alveolar macrophage relative count in infected animals from 60 to 330 dpi. This study shows that the BAL is an accurate technique for the diagnosis of canine angiostrongylosis. Moreover, the technique allows us to retrieve cells and other elements that line the lung surface for cytological evaluation, which provides information about inflammatory diseases, and the diagnosis and prognosis of pulmonary parasites such as A. vasorum.
Assuntos
Angiostrongylus/isolamento & purificação , Líquido da Lavagem Broncoalveolar , Doenças do Cão/diagnóstico , Infecções por Strongylida/veterinária , Análise de Variância , Angiostrongylus/citologia , Animais , Lavagem Broncoalveolar/métodos , Lavagem Broncoalveolar/veterinária , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/parasitologia , Estudos de Casos e Controles , Doenças do Cão/imunologia , Doenças do Cão/parasitologia , Cães , Eosinófilos/citologia , Neutrófilos/citologia , Infecções por Strongylida/diagnóstico , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia , Fatores de TempoRESUMO
The present study was carried out to investigate the immune response against Strongyloides venezuelensis infection in Balb/c mice previously immunized with larva-antigens or primed with live-larvae. Our results indicate that all primed mice developed a strong protection against challenge infection that remained active for 45 days. In mice primed with live-larvae the challenge infection resulted in great reduction of migrating larvae and the worms were completely eliminated from the small intestine before maturation. The protection pattern did not alter when the primary infection was aborted by drug treatment. In these experimental groups, the challenge infection was accompanied by a type-2 predominant immune response, intense IgE and reactive IgG1 production, and granulocyte infiltration in skin, lungs and intestine. The challenge infection in antigen-immunized mice also resulted in great reduction of migrating larvae. However, the worms that reached the host intestine matured, produced eggs and were eliminated similarly to the ones from nonimmunized mice. Protective mechanisms after immunization with larva antigen were migrating larva-specific and associated with a strong and mixed Th1 and Th2 response, without tissue granulocyte infiltration. In conclusion, protective immunity induced by a previous infection or antigen-immunization are stage-specific and operate through different effector mechanisms.