Research on the Regulatory Effects of Resveratrol on BCG-Induced Autophagy and Apoptosis in Macrophages via Targeting SIRT1

Abstract

Mycobacterium tuberculosis (Mtb) infection can trigger immune responses in macrophages during its autophagy and apoptosis, as two crucial cellular processes which are essential for the host to clear the pathogen. Resveratrol (RES) is a natural polyphenolic compound with various biological functions such as anti-inflammatory, antioxidant, and immunomodulatory activities. However, the specific mechanism by which it regulates autophagy and apoptosis in a Bacillus Calmette-Guérin (BCG)-infected macrophage model remains to be elucidated. This study aimed to analyze the effects of RSE on BCG-induced autophagy and apoptosis in macrophages and explore the underlying molecular mechanisms. The mouse macrophage cell line RAW264.7 was used to establish a BCG infection model and evaluate the interventional effects of RES. Cell viability was detected by CCK-8 assay. The expression levels of autophagy- and apoptosis-related proteins were analyzed by Western blotting. LC3 puncta formation was observed by immunofluorescence. Autophagy rate and apoptosis rate were determined by flow cytometry. The ultrastructure of autophagosomes and autolysosomes was observed by transmission electron microscopy. The results showed that BCG infection significantly increased the expression of LC3-II, Beclin1, Atg5, and Atg7 in macrophages; decreased p62 levels; and increased the number of intracellular autophagosomes and autolysosomes. Concurrently, BCG infection also induced apoptosis, including upregulation of Bax, Caspase 3, Caspase 9, and PARP1 expression; downregulation of Bcl-2 expression; and an increased apoptosis rate. RES promoted autophagosome accumulation and inhibited apoptosis in BCG-infected macrophages in a concentration-dependent manner; however, these effects were significantly attenuated after SIRT1 gene silencing by siRNA and inhibition by EX527. Therefore, it is speculated that RES may regulate autophagy and apoptosis through the SIRT1/FOXO1 pathway. These findings provide a potential experimental basis for developing RES into a host-directed therapeutic (HDT) agent, and offer new insights into the mechanisms by which natural products participate in host defense.

The authors' abstract, as published at the source. Microorganisms, 2026 · DOI ↗