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ABSTRACT: Immunomodulatory properties have been described for Fasciola hepatica excretory-secretory products (FhESP), with their interaction with the innate immune cells being crucial during the early stages of infection. Previously, we demonstrated that FhESP induce eosinophil apoptosis. In this work, the ability of FhESP to induce apoptosis of peritoneal macrophages was evaluated. These parasite products were observed to induce apoptosis in peritoneal macrophages stimulated in vitro with FhESP, as well as in cells recovered from infected mice. The ability of FhESP to modify the viability of macrophages by apoptosis induction may constitute a crucial event for extending its survival in the host.
Veterinary Immunology and Immunopathology 07/2012; 148(3-4):359-63. · 2.08 Impact Factor
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ABSTRACT: Fasciola hepatica releases excretory-secretory products (FhESP), and immunomodulatory properties have been described for the carbohydrates present in these parasite products. The interaction of FhESP with the innate immune cells, such as macrophages, is crucial in the early stage of infection. In this work we observed that peritoneal macrophages from naive BALB/c mice stimulated in vitro with FhESP presented: an increased arginase activity as well as Arginase I expression, and high levels of transforming growth factor-β and interleukin-10. A similar macrophage population was also observed in the peritoneum of infected mice. A partial inhibition of the immunomodulatory effects described above was observed when macrophages were pre-incubated with Mannan, anti-mannose receptor, Laminarin or anti-Dectin-1, and then stimulated with FhESP. In addition, we observed a partial inhibition of these effects in macrophages obtained from mice that were intraperitoneally injected with Mannan or Laminarin before being infected. Taken together, these results suggest the participation of at least two C-type lectin receptors, mannose receptor and Dectin-1, in the interaction of FhESP with macrophages, which allows this parasite to induce immunoregulatory effects on these important innate immune cells and may constitute a crucial event for extending its survival in the host.
Immunology 07/2011; 133(3):386-96. · 3.32 Impact Factor
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ABSTRACT: Eosinophils (Eo) are typically associated with immune response to helminth. Previously, we demonstrated that excretory-secretory products (ESP) from Fasciola hepatica induce eosinophil apoptosis by a caspase-dependent mechanism. In this study, we observed that ESP caused mitochondrial-membrane depolarization of eosinophils leading to the release of cytochrome c. Also, ESP induced an increase in the reactive oxygen species (ROS) production, which preceded the mitochondrial injury. We found a significant rise in hydrogen peroxide, but not in the anion superoxide levels. Furthermore, catalase, but not superoxide dismutase, inhibited the mitochondrial depolarization as well as apoptosis. So, ESP induce in Eo an early increase in the ROS production, mainly hydrogen peroxide, which precedes mitochondrial injury and leads again to apoptosis. Finally, we demonstrated the participation of hydrogen peroxide in the peritoneal Eo apoptosis in vivo, both during the early stages of experimental fasciolosis in rats and after intraperitoneal ESP treatment.
Molecular and Biochemical Parasitology 12/2008; 163(2):95-106. · 2.55 Impact Factor
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ABSTRACT: Eosinophils (Eo) are known to be important effector cells in the host defense against helminth parasites. Excretory-secretory products (ESP) released by helminths have shown wide immunomodulatory properties, such as the induction of cellular apoptosis. We investigated the ability of ESP from Fasciola hepatica to induce Eo apoptosis. In this work, we observed that ESP induced an early apoptosis of rat peritoneal eosinophils and that this phenomenon was time- and concentration-dependent. Furthermore, we demonstrated that activation of protein tyrosine kinases (TyrK) and caspases were necessary to mediate the Eo apoptosis induced by the ESP, and that carbohydrate components present in these antigens were involved in this effect. We have described for the first time the ability of ESP from F. hepatica to modify the viability of Eo by apoptosis induction. Besides that, we have observed Eo apoptosis in the liver of rats 21 days after F. hepatica infection. The diminution in Eo survival in early infection could be a parasite strategy in order to prevent a host immune response.
Veterinary Immunology and Immunopathology 07/2007; 117(3-4):197-208. · 2.08 Impact Factor
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ABSTRACT: Fasciola hepatica is a trematode that affects human and domestic ruminant health, causing significant economic losses in cattle estimated at US$2000 millon per year. Juvenile parasites migrating through the host tissues, as well as adults settle in the biliary ducts, are in contact with different cells from the immune system. Despite those interactions, the persistence of the parasite in the host for many years provides evidence of its ability to prevent or down-modulate the inflammatory response in the infection site. Different strategies have been developed by the parasite to prevent potential damage being induced by the immune response, thus allowing some parasites to reach the adult stage in a safe place such as the biliary ducts. In this review we discuss how excretory-secretory products (ESP) from F. hepatica can affect the functionality of pivotal immune cells, such as eosinophils and macrophages by inducing selective apoptosis pathways and alternative activation of macrophages. Furhermore, the modulatory effects of ESP on dendritic cell activation and lymphocyte proliferation is reviewed as a strategy to facilitate F. hepatica evasion of both innate and adaptive immunity.
