EaMIC3 inhibits cell apoptosis and facilitates Eimeria acervulina infection through interacting with EpCAM

Abstract

Coccidiosis, caused by Eimeria acervulina, is a pathogenic protozoan disease, leading to huge economic losses to the global poultry industry. At the early stage of E. acervulina infection, microneme protein 3 (EaMIC3) is involved in the inhibition of infected host cell apoptosis, but the underlying mechanisms remain unclear. Here, EaMIC3 was shown to inhibit the apoptosis of infected host cells and facilitate parasite infection by interacting with epithelial cell adhesion molecule (EpCAM). This interaction was mediated by binding of three microneme adhesive repeat regions (MAR) 1, 2, and 5 in EaMIC3 to EpEX, an extracellular domain cleaved from EpCAM. During infection, EaMIC3 regulated the expression of both EpCAM and EpEX, with EpEX in turn inhibiting apoptosis of infected duodenal epithelial cells through the EGFR/Akt/mTOR pathway. Moreover, EpCAM knockdown inhibited sporozoite infection, while EpCAM overexpression promoted sporozoite infection. Consistently, the administration of pooled EaMIC3 and EpCAM antisera conferred a good therapeutic effect on E. acervulina infection in chicks, with a maximum oocyst reduction rate of 67.86%. These findings reveal a mechanism by which EaMIC3 inhibits cell apoptosis and facilitates E. acervulina infection. The therapeutic efficacy of EaMIC3 and EpCAM antibodies may further be exploited for prevention and control of coccidiosis in chicks. Eimeria acervulina microneme protein 3 (EaMIC3) promotes parasite infection by interacting with EpCAM/EpEX to suppress host cell apoptosis. Targeting EaMIC3 and EpCAM reduced infection in chicks, highlighting their potential as therapeutic targets for coccidiosis control.