Extracellular vesicles released by host epithelial cells during Pseudomonas aeruginosa infection function as homing

Rajalakshmy Ayilam Ramachandran1, Andrew Lemoff2, Danielle M Robertson3,4

  • 1The Departments of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.

Abstract

Insights

Extracellular vesicles (EVs) from Pseudomonas aeruginosa (PA) infected eye and lung cells drive neutrophil migration. These host-derived EVs are key mediators of the immune response during PA infections.

Area of Science:

  • Microbiology and Immunology
  • Cell Biology
  • Extracellular Vesicle Research

Background:

  • Pseudomonas aeruginosa (PA) is an opportunistic pathogen causing severe eye and lung infections.
  • Host-derived extracellular vesicles (EVs) role in PA infection is understudied.
  • Investigating host EVs' composition and function in PA infection is crucial.

Purpose of the Study:

  • To profile the composition of host-derived EVs during PA infection.
  • To determine the functional capacity of these EVs in modulating innate immune responses.
  • To compare EV characteristics from corneal versus bronchial epithelial cells.

Main Methods:

  • Human corneal (hTCEpi) and bronchial (HBECs) epithelial cells infected with PAO1.
  • Isolation of host-derived EVs using size exclusion chromatography.
  • Proteomic analysis via mass spectrometry and functional assays with immune cells.

Main Results:

  • EVs from infected corneal cells increased pro-inflammatory cytokines and induced neutrophil chemotaxis.
  • EVs from infected bronchial cells induced neutrophil chemotaxis but not cytokine secretion.
  • Proteomic analysis revealed lower complexity in EVs from corneal cells compared to bronchial cells.

Conclusions:

  • This study first comprehensively profiles EVs from PA-infected corneal and bronchial epithelial cells.
  • Host-derived EVs are potent mediators of neutrophil migration during PA infection.
  • EVs contribute significantly to the neutrophil response in ocular and pulmonary PA infections.

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