Naturally Produced Outer Membrane Vesicles from Pseudomonas aeruginosa Elicit a Potent Innate Immune Response

A newly published report in Infection and Immunity reveals that naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components. Researchers in the United States characterized the inflammatory responses to these vesicles and determined the contribution of vesicle Toll-like receptor (TLR) ligands and vesicle proteins to that response. The study found that intact vesicles elicit a profoundly greater inflammatory response than the response to purified lipopolysaccharide (LPS), and that both TLR ligands LPS and flagellin contributed to specific vesicle cytokine responses.

Key Takeaways:

• Intact vesicles elicit a profoundly greater inflammatory response than the response to purified lipopolysaccharide (LPS), indicating a synergistic effect between LPS and protein components.
• Both TLR ligands LPS and flagellin contributed to specific vesicle cytokine responses, whereas the CpG DNA content of vesicles did not.
• Neutralization of LPS sensing demonstrated that macrophage responses to the protein composition of vesicles required the adjuvantlike activity of LPS to elicit strain-specific responses.
• Protease treatment to remove proteins from the vesicle surface resulted in decreased interleukin-6 and tumor necrosis factor-alpha production, indicating that the production of these specific cytokines may be linked to macrophage recognition of vesicle proteins.
• Confocal microscopy of vesicle uptake by macrophages revealed that vesicle LPS allows for binding to macrophage surfaces, whereas vesicle protein content is required for internalization.
• The researchers concluded that macrophage sensing of both LPS and protein components of outer membrane vesicles combine to produce a bacterial strain-specific response that is distinct from those triggered by individual, purified vesicle components.

Statistics:

• 3822-31: The page numbers of the published study in Infection and Immunity.
• 78(9): The issue number of the published study in Infection and Immunity.
• 2010: The year the study was published.

Sources:

• Ellis, T.N., et al. (2010). Naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components. Infection and Immunity, 78(9), 3822-31.
• T.N. Ellis, Duke University Medical Center, Dept. of Biochemistry, Box 3711, Durham, NC 27710 USA.