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Ferreira, H. B.

Publications and source records attributed to Ferreira, H. B..

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New insights of the local immune response against both fertile and infertile hydatid cysts

BackgroundCystic echinococcosis is caused by the metacestode of the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, the metacestode grows as a unilocular cyst known as hydatid cyst. This cyst is comprised of two layers of parasite origin: germinal and laminated layers, and one of host origin: the adventitial layer, that encapsulates the parasite. This adventitial layer is composed of collagen fibers, epithelioid cells, eosinophils and lymphocytes. To establish itself inside the host, the germinal layer produces the laminated layer, and to continue its life cycle, generates protoscoleces. Some cysts are unable to produce protoscoleces, and are defined as infertile cysts. The molecular mechanisms involved in cyst fertility are not clear, however, the host immune response could play a crucial role.\n\nMethodology/Principal fidingsWe collected hydatid cysts from both liver and lungs of slaughtered cattle, and histological sections of fertile, infertile and small hydatid cysts were stained with haematoxylin-eosin. A common feature observed in infertile cysts was the disorganization of the laminated layer by the infiltration of host immune cells. These infiltrating cells eventually destroy parts of laminated layer. Immunohistochemical analysis of both parasite and host antigens, identify these cells as cattle macrophages and are present inside the cysts associated to germinal layer.\n\nConclusions/SignificanceThis is the first report that indicates to cell from immune system present in adventitial layer of infertile bovine hydatid cysts could disrupt the laminated layer, infiltrating and probably causing the infertility of cyst.\n\nAuthor SummaryCystic echinococcosis is caused by the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, mainly liver and lungs of herbivores such as cows and sheep as well as human beings, the parasite grows as a unilocular cyst known as hydatid cyst. These cysts develop in their inner chamber a structure known as protoscolex, when consumed by the definitive host (e.g. dogs), it grows into a worm that resides in the small intestine and produces eggs that contaminate the environment. In cattle, most hydatid cysts are unable to produce protoscoleces, and thus are termed infertile hydatid cysts. The molecular mechanisms that explain the causes of hydatid cyst infertility remain unknown. We routinely collected cattle hydatid cysts from both liver and lugs and processed them for histological analysis. We found that there is a subset of fertile hydatid cysts that have low protoscolex viability and high immune infiltration surrounding the cyst. All infertile cysts have high immune infiltration, and many of them show disruption of the laminated layer and immune cells of host origin inside the cyst. This is the first report that shows that the cyst can be infiltrated by the host immune system.

immunology

Antigen B from Echinococcus granulosus enters mammalian cells by endocytic pathways

Cystic hydatid disease is a zoonosis caused by the larval stage (hydatid cyst) of Echinococcus granulosus (Cestoda, Taeniidae). The hydatid cyst develops in the viscera of intermediate host as a unilocular structure filled by the hydatid fluid, which contains parasitic excretory/secretory products. Antigen B (AgB) is the major component of E. granulosus metacestode hydatid fluid. Functionally, AgB has been implicated in immunomodulation and lipid transport. However, the mechanisms underlying AgB functions are not completely known. In this study, we investigated AgB interactions with different mammalian cell types and the pathways involved in its internalization. AgB uptake was observed in four different cell lines, NIH-3T3, A549, J774 and RH. Inhibition of raft-mediated endocytosis causes about 50 and 69% decrease in AgB internalization by RH and A549 cells, respectively. Interestingly, AgB colocalized with the raft endocytic marker, but also showed a partial colocalization with the clathrin endocytic marker. The results indicate that raft-mediated endocytosis is the main route to AgB internalization, and that a clathrin-mediated entry may also occur at a lower frequency. Cellular internalization could be a requirement for AgB functions as a lipid carrier and/or immunomodulatory molecule, contributing to create a more permissive microenvironment to metacestode development and survival.\n\nAuthor summaryAntigen B (AgB) is an oligomeric lipoprotein highly abundant in Echinococcus granulosus hydatid fluid. AgB has already been characterized as an immunomodulatory protein, capable of inducing a permissive immune response to parasite development. Also, an important role in lipid acquisition is attributed to AgB, because it has been found associated to different classes of host lipids. However, the mechanisms of interaction employed by AgB to perform its functions remain undetermined. In this study, we demonstrate that mammalian cells are able to internalize E. granulosus AgB in culture and found that specific mechanisms of endocytosis are involved. Our results extend the understanding of AgB biological role indicating cellular internalization as a mechanism of interaction, which in turn, may represent a target to intervention.

molecular biology