Deletion of the Type IV Secretion System Effector VceA Promotes Autophagy and Inhibits Apoptosis in Brucella-Infected Human Trophoblast Cells.

Brucellosis is the most common zoonotic disease that caused by intracellular parasitic bacteria Brucella. The survival and replication of Brucella in the host depend on the type IV secretion system (T4SS). The T4SS system of Brucella has many components and secreted proteins. But the mechanism helped Brucella to evade the host defense is still not clear. The objective of the present study was to investigate the effects of VceA on autophagy and apoptosis in Brucella-infected embryonic trophoblast cells. We constructed the VceA mutant strain (2308ΔVceA) and complementary strain (2308ΔVceA-C) of Brucella abortus 2308 (S2308). The human trophoblast cells (HPT-8 cells) and mice were infected by S2308, 2308ΔVceA and 2308ΔVceA-C. The cell autophagy and apoptosis were detected. The Atg5, LC3-II and Bcl-2 mRNA expression were significantly increased in 2308ΔVceA group than the S2308 group, and mRNA expression of P62 and Caspase-3 were significantly decreased than the S2308 group. Western blotting, qPCR and flow cytometry analysis showed that 2308ΔVceA promoted autophagy and inhibited apoptosis. Mouse immunohistochemistry experiments showed that P62 protein was scattered coloring and Cytochrome C protein was scarcely in 2308ΔVceA group at the myometrium. These results indicated that 2308ΔVceA promoted autophagy and inhibited apoptosis in HPT-8 cells during Brucella infection.