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.

Archives of Microbiology
|February 10, 2025
PubMed

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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