Enolase of Streptococcus Suis Serotype 2 Enhances Blood-Brain Barrier Permeability by Inducing IL-8 Release

Area of Science:

• Neuroscience
• Infectious Diseases
• Microbiology

Background:

• Streptococcus suis serotype 2 (SS2) is a growing zoonotic pathogen.
• Meningitis is the most common clinical presentation of SS2 infection.
• The precise role of the SS2 virulence factor, enolase (Eno), in meningitis pathogenesis remains unclear.

Purpose of the Study:

• To investigate the mechanism by which SS2 enolase (Eno) contributes to meningitis.
• To determine Eno's effect on blood-brain barrier (BBB) integrity and associated inflammatory responses.

Main Methods:

• Utilized an in vitro Transwell co-culture model of the BBB with porcine brain microvascular endothelial cells (PBMECs) and astrocytes (ACs).
• Expressed Eno inducibly and assessed its impact on BBB permeability and cytokine release (e.g., IL-8).
• Employed mouse models to evaluate Eno's effects on BBB permeability (Evans blue assay) and IL-8 levels, with and without an IL-8 receptor antagonist (G31P).

Main Results:

• Eno significantly increased BBB permeability and promoted the release of IL-8 and other cytokines in vitro.
• IL-8 was found to significantly compromise the integrity of the in vitro BBB model.
• In vivo, Eno administration in mice led to increased Evans blue extravasation into the brain and elevated serum and brain IL-8 levels.
• Treatment with the IL-8 receptor antagonist G31P reduced Evans blue concentration in the brains of Eno-treated mice.

Conclusions:

• SS2 enolase (Eno) plays a significant role in disrupting BBB integrity during meningitis.
• Eno facilitates this disruption primarily by inducing the release of IL-8.
• Targeting the Eno-IL-8 pathway presents a potential therapeutic strategy for SS2 meningitis.