Mechanistic and transcriptomic study reveals TSPO modulates TLR4-driven inflammatory signaling and metabolic adaptation in immune cells, highlighting its potential as a therapeutic target.
Key Points
To investigate the role and molecular mechanisms of mitochondrial translocator protein (TSPO) in Toll-like receptor 4 (TLR4)-mediated inflammation and immunometabolic adaptation.
Analyzed human peripheral blood transcriptomic data (GSE72829) across bacterial infection (n = 52), viral infection (n = 92), and healthy controls (n = 16), alongside single-cell profiles from CELLxGENE.
Performed in vitro functional and mechanistic assays using BV2 microglia and RAW264.7 macrophage cell models.
TSPO was significantly upregulated in bacterial infection compared to viral infection and healthy controls, showing diagnostic utility.
TSPO physically interacted with TLR4 to selectively regulate downstream inflammatory activation pathways.
TSPO deficiency amplified LPS-induced TNF-α and IL-6 release, disrupted Ca2+ homeostasis and cholesterol balance, and induced metabolic remodeling with elevated L-lactate and sustained ATP levels.