Autophagy-Mediated Immune Evasion in Entamoeba histolytica: Molecular Mechanisms and Host Cell Interactions

Abstract

Entamoeba histolytica is a protozoan parasite responsible for amebiasis, affecting approximately 50 million people globally. The parasite employs sophisticated molecular mechanisms to evade host immune responses, with autophagy playing a crucial role. This study investigates autophagy-mediated immune evasion mechanisms in E. histolytica, focusing on the Atg8 conjugation system. We examined E. histolytica trophozoites under various stress conditions and analyzed Atg8 expression, localization, and function during host cell interaction. Results demonstrate that EhAtg8 is constitutively expressed and significantly upregulated during host cell contact. Immunofluorescence revealed distinct Atg8-positive structures associated with phagosomes containing host cell fragments. Gene silencing of EhAtg8 resulted in impaired phagosome acidification and reduced cytotoxicity toward human colonic epithelial cells. Proteomic analysis identified 127 Atg8-interacting proteins involved in vesicular trafficking, immune evasion, and nutrient acquisition. The study reveals that autophagy in E. histolytica differs from canonical starvation-induced autophagy, functioning primarily in host cell exploitation. Our findings suggest that EhAtg8 mediates degradation of host immune effector molecules and facilitates parasite survival. These results provide novel insights into parasite-host interactions and identify potential therapeutic targets for amebiasis treatment.