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

Background Coccidiosis caused by Eimeria species is a deadly parasitic disease particularly affecting chicks, leading to huge economic losses to the global poultry industry. The mechanisms underlying parasite infection remain poorly understood. Results Here, we showed that Eimeria acervulina microneme protein 3 (EaMIC3) was involved in the apoptosis of infected host cells and parasite infection by interacting with epithelial cell adhesion molecule (EpCAM). The interaction was mediated by the 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 signaling pathway. Moreover, EpCAM knockdown inhibited sporozoite infection, while EpCAM overexpression promoted sporozoite infection. Conclusion Consistently, the administration of pooled EaMIC3 and EpCAM antisera conferred a good therapeutic effect on E. acervulina infection in chickens, with a maximum oocyst reduction rate of 67.86%. Overall, these findings reveal a mechanism by which EaMIC3 inhibits cell apoptosis and facilitates E. acervulina infection, shedding light on the prevention and control of coccidiosis in chickens.