Antigen B from Echinococcus granulosus enters mammalian cells by endocytic pathways.

Edileuza Danieli Da Silva,Arnaldo Zaha,Henrique Bunselmeyer Ferreira,Martin Cancela,Karina Mariante Monteiro,Wenbao Zhang

doi:10.1371/journal.pntd.0006473

Edileuza Danieli Da Silva, Arnaldo Zaha + Show 4 more

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https://doi.org/10.1371/journal.pntd.0006473

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Abstract

BackgroundCystic hydatid disease is a zoonosis caused by the larval stage (hydatid) of Echinococcus granulosus (Cestoda, Taeniidae). The hydatid develops in the viscera of intermediate host as a unilocular structure filled by the hydatid fluid, which contains parasitic excretory/secretory products. The lipoprotein 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.Methodology/Principal findingsIn 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 caveolae/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. Finally, AgB colocalized with an endolysosomal tracker, providing evidence for a possible AgB destination after endocytosis.Conclusions/SignificanceThe results indicate that caveolae/raft-mediated endocytosis is the main route to AgB internalization, and that a clathrin-mediated entry may also occur at a lower frequency. A possible fate for AgB after endocytosis seems to be the endolysosomal system. Cellular internalization and further access to subcellular compartments 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.

Highlights

Cystic hydatid disease (CHD), caused by the larval stage of parasites belonging to the Echinococcus granulosus sensu lato (s.l.) complex, is a zoonosis of worldwide occurrence, with a considerable medical and economic impact [1]
We demonstrate that mammalian cells are able to internalize E. granulosus Antigen B (AgB) in culture and found that specific mechanisms of endocytosis are involved
We investigated the ability of hydatid fluid (HF)-purified AgB to enter into different mammalian cell types in vitro, and the mechanisms involved in AgB internalization

Summary

Introduction

Cystic hydatid disease (CHD), caused by the larval stage (hydatid or metacestode) of parasites belonging to the Echinococcus granulosus sensu lato (s.l.) complex, is a zoonosis of worldwide occurrence, with a considerable medical and economic impact [1]. The adult tapeworm lives in the small intestine of a definitive canid host, and the larval stage develops in the viscera of a wide range of mammal species, including humans. Protoescoleces are the pre-adults, infective to the definitive host, which remain quiescent and immersed in the hydatid fluid (HF), which is a complex mixture of molecules of both host and parasite origin. The hydatid develops in the viscera of intermediate host as a unilocular structure filled by the hydatid fluid, which contains parasitic excretory/secretory products. The mechanisms underlying AgB functions are not completely known

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