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Published on: May 3, 2024
Outer membrane vesicles from Pseudomonas aeruginosa induce autophagy-regulated pyroptosis in THP-1 cells
Jing Ge1,2, Yaoyang Liu1,2, Tianqi Wu3
1Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, P.R. China.
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.
Insights
Pseudomonas aeruginosa outer membrane vesicles (PA-OMVs) impact immune responses by modulating autophagy and pyroptosis. Inhibiting autophagy reduced pyroptosis, suggesting a therapeutic target for infections.
Area of Science:
- Microbiology and Immunology
- Cellular Biology
- Pathogen-Host Interactions
Background:
- Outer membrane vesicles (OMVs) from Pseudomonas aeruginosa (PA-OMVs) are key virulence factors involved in immune modulation and inflammation.
- Autophagy and pyroptosis are critical cellular processes regulating immune responses and host defense against infections.
- The interplay between PA-OMVs, autophagy, and pyroptosis is not well understood, hindering the development of targeted therapies.
Purpose of the Study:
- To investigate the influence of PA-OMVs on cellular autophagy and pyroptosis.
- To elucidate the regulatory mechanisms governing these interactions.
- To identify potential therapeutic strategies for infectious diseases by targeting the autophagy-pyroptosis axis.
Main Methods:
- Bulk RNA sequencing and bioinformatics analysis of PA-OMV-treated cells.
- Utilizing autophagy inhibitors (chloroquine, 3-methyladenine) to assess pyroptosis.
- Employing RT-PCR and ELISA to quantify pyroptosis levels.
Main Results:
- PA-OMVs were found to modulate key immune and inflammatory pathways.
- A complex interplay between autophagy and pyroptosis was observed.
- Inhibition of autophagy led to decreased expression of pyroptosis markers, indicating a regulatory role.
Conclusions:
- The autophagy-pyroptosis axis is significantly influenced by PA-OMVs.
- Targeting this axis presents a promising avenue for novel infection control strategies.
- Findings support the potential for developing new vaccines and therapeutics based on modulating these cellular processes.
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