Mechanistic Insights into Eimeria tenella-Induced Host Cell Apoptosis Through Modulation of the Mitochondrial Permeability Transition Pore

通过调节线粒体通透性转换孔揭示柔嫩艾美球虫诱导宿主细胞凋亡的机制

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Abstract

Coccidiosis due to Eimeria tenella remains a major constraint on the poultry industry. Previous studies have revealed that E. tenella infection triggers apoptosis in host cells. The mitochondrial permeability transition pore (MPTP) plays a pivotal role in the apoptosis and necrosis observed in infected host cells. However, the effect of MPTP opening on mitochondrial apoptotic factors remains unclear. To elucidate the dynamic changes in apoptotic signals during MPTP-mediated apoptosis in host cells infected with E. tenella, we established a chicken embryo caecal epithelial cell infection model. Cyclosporin A (CsA) was used to inhibit the MPTP. The infection rate was assessed by Hematoxylin and eosin (H&E) staining, whereas MPTP opening and the abundances of the mitochondrial apoptotic factors Smac, Endo G, and AIF were determined by flow cytometry and ELISA, respectively. The results revealed that both the degree of MPTP opening was markedly reduced in the E. tenella+CsA group compared to the E. tenella group (p < 0.05). Between 24 and 120 h post-infection (hpi), the cytoplasmic levels of Smac, Endo G, and AIF were significantly elevated in the E. tenella group compared with the control group (p < 0.05), while their mitochondrial levels were markedly decreased (p < 0.05). In contrast, mitochondrial expression of these factors was restored in the E. tenella+CsA group (p < 0.05), accompanied by a reduction in their cytoplasmic abundance (p < 0.05). These findings indicate that E. tenella promotes MPTP-dependent release of mitochondrial pro-apoptotic factors into the cytosol during the mid-to-late stages of infection, whereas pharmacological inhibition of the MPTP limits this redistribution.

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