Significant apoptosis rather autophagy predominates in astrocytes caused by Toxocara canis larval excretory-secretory antigens

• Main Authors: Chia-Mei Chou, Chia-Kwung Fan
• Format: Article
• Language: English
• Published: Elsevier 2020-04-01
• Series: Journal of Microbiology, Immunology and Infection
• Online Access: http://www.sciencedirect.com/science/article/pii/S1684118218302238

Background/purpose: Toxocariasis is a worldwide parasitic zoonosis and mainly caused by Toxocara canis. Humans can be infected by accidental ingestion of T. canis embryonated ova through contacting with contaminated food, water, or encapsulated larvae in paratenic hosts' viscera or meat. Since humans are the paratenic host of T. canis, the wandering and neuroinvasive larvae can cause mechanical tissue damage and the excretory-secretory antigens (TcES Ag) might induce neuroinflammatory responses in the brain. Human cerebral toxocariasis (CT) has been reported to cause several neurological symptoms and may develop into neurodegenerative diseases. However, the roles of astrocytes involved in the pathogenesis of CT remained largely unclear. Methods: This study intended to investigate the cytotoxic effects of TcES Ag on astrocytes as assessed by apoptosis and autophagy expression. Results: Our results showed TcES Ag treatment reduced cell viability and caused morphological changes. Expressions of autophagy associated proteins including Beclin 1, phosphor-mTOR and LC3-Ⅱ were not significantly changed; however, p62 as well as the cell survival protein, mTOR, was concomitantly decreased in TcES Ag treatment. Significantly accelerated cleaved caspase-3 and cytochrome c expression as well as enhanced caspase-9 and caspase-8 activation were found in astrocytes with TcES Ag treatment. Caspase-3 activity and apoptotic cells numbers were also increased as detected by fluorescence microscopy. Conclusion: We concluded that TcES Ag may trigger astrocytes apoptosis predominantly through intrinsic and extrinsic pathways rather autophagy, revealing a novel role of astrocytes in the pathogenesis of CT. Keywords: Astrocyte, T. canis excretory-secretory antigens, Apoptosis, Autophagy, Cerebral toxocariasis