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

Abstract

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.