4.4 Article

Pseudomonas aeruginosa-Derived Extracellular Vesicles Modulate Corneal Inflammation: Role in Microbial Keratitis?

Journal

INFECTION AND IMMUNITY
Volume 91, Issue 4, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/iai.00036-23

Keywords

keratitis; Pseudomonas aeruginosa; extracellular vesicles; neutrophils; innate immunity; innate immune system

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Pseudomonas aeruginosa keratitis occurs in individuals who have suffered trauma, in immunocompromised patients, and in otherwise healthy individuals who wear contact lenses. It is characterized by a light-blocking infiltrate and is the most severe complication associated with contact lens wear, potentially leading to vision loss.
Pseudomonas aeruginosa keratitis occurs following trauma, in immunocompromised patients, and in otherwise healthy contact lens wearers. Characterized by a light-blocking infiltrate, P. aeruginosa keratitis is the most serious complication associated with contact lens wear and, in severe cases, can lead to vision loss. Bacterial extracellular vesicles (B EVs) are membrane-enclosed nanometer-scale particles secreted from bacteria and are packed with bioactive molecules. B EVs have been shown to mediate biological functions that regulate host pathogenic responses. In the present study, we isolated P. aeruginosa-derived EVs using size exclusion chromatography and compared the proteomic compositions and functional activities of P. aeruginosa-derived EVs and P. aeruginosa-derived free protein (FP) on corneal epithelial cells and neutrophils. Importantly, P. aeruginosa-derived EVs and FP exhibited unique protein profiles, with EVs being enriched in P. aeruginosa virulence proteins. P. aeruginosa-derived EVs promoted corneal epithelial cell secretion of interleukin-6 (IL-6) and IL-8, whereas these cytokines were not upregulated following treatment with FP. In contrast, FP had a negative effect on the host inflammatory response and impaired neutrophil killing. Both P. aeruginosa-derived EVs and FP promoted intracellular bacterial survival in corneal epithelial cells. Collectively, these data suggest that P. aeruginosa-derived EVs and FP may play a critical role in the pathogenesis of corneal infection by interfering with host innate immune defense mechanisms. Pseudomonas aeruginosa keratitis occurs following trauma, in immunocompromised patients, and in otherwise healthy contact lens wearers. Characterized by a light-blocking infiltrate, P. aeruginosa keratitis is the most serious complication associated with contact lens wear and, in severe cases, can lead to vision loss.

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