Resveratrol triggers autophagy-dependent apoptosis via suppressing the PI3K/AKT/mTOR pathway in Chlamydia psittaci-infected cells.

Chlamydia psittaci, a zoonotic pathogen, promotes its intracellular survival by dysregulating host cell death pathways. This study demonstrates that resveratrol (Res), a natural polyphenol, counteracts this pathogenic strategy in infected human bronchial epithelial (HBE) cells by inducing autophagy-dependent apoptosis. Res exhibited excellent biocompatibility, maintaining cell viability above 85% at concentrations ≤100 μmol/L after 24 h treatment. Within this non-cytotoxic range, Res significantly inhibited C. psittaci growth in dose- and time-dependent manners, with maximal effect at 100 μmol/L after 24 h. Mechanistically, Res enhanced autophagic flux in infected cells, evidenced by increased LC3 puncta formation, upregulation of Beclin-1 and LC3-II, and downregulation of p62. Concurrently, Res induced apoptosis, characterized by elevated Bax/Bcl-2 ratio and enhanced Cleaved Caspase-3 expression. Pharmacological (3-Methyladenine, 3-MA) or genetic (Beclin-1/LC3B silencing) inhibition of autophagy significantly attenuated Res-induced apoptosis, confirming an autophagy-dependent mechanism. Res also suppressed PI3K/AKT/mTOR phosphorylation in infected cells, and pathway reactivation with 740Y-P reversed its pro-autophagic and pro-apoptotic effects. Collectively, these findings demonstrate that resveratrol induced autophagy-dependent apoptosis through suppression of the PI3K/AKT/mTOR pathway in C. psittaci-infected cells, highlighting its therapeutic potential against intracellular pathogens.