Outer membrane vesicles from Pseudomonas aeruginosa induce autophagy-regulated pyroptosis in THP-1 cells

Outer membrane vesicles derived from Pseudomonas aeruginosa (PA-OMVs) play a crucial role in Bacterial pathogenesis, mediating immune modulation and inflammation. Autophagy, a process that degrades damaged organelles, and Pyroptosis, a form of programmed cell death, both regulate immune responses and contribute to Infection defense. However, the relationship between PA-OMVs, Autophagy, and Pyroptosis remains insufficiently explored, particularly regarding their regulatory mechanisms. This study investigates how PA-OMVs influence cellular Autophagy and Pyroptosis, with the aim of identifying potential therapeutic strategies for infectious diseases. Bulk RNA Sequencing and bioinformatics analysis were conducted on cells treated with PA-OMVs. Autophagy inhibitors, chloroquine (CQ) and 3-methyladenine (3-MA), were used to explore their effects on Pyroptosis, with RT-PCR and ELISA applied to assess Pyroptosis levels. The results revealed a complex interplay between Autophagy and Pyroptosis, with PA-OMVs modulating key immune and inflammatory pathways. Autophagy inhibition decreased the expression of Pyroptosis markers, suggesting a regulatory role. These findings highlight the potential of targeting the autophagy-pyroptosis axis for new Infection control strategies and vaccine development.