Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration

Area of Science:

• Microbiology
• Immunology
• Neuroscience

Background:

• Group B Streptococcus (GBS) is a primary cause of meningitis in neonates.
• Bacterial pili, including GBS pili, are crucial for pathogen-host interactions.
• The specific role of GBS pilus tip adhesin PilA in central nervous system (CNS) disease remains unclear.

Purpose of the Study:

• To elucidate the host receptor for GBS PilA.
• To determine the contribution of PilA to GBS pathogenesis in the CNS.
• To investigate the mechanism by which PilA facilitates CNS invasion.

Main Methods:

• Binding assays to identify PilA's host receptor.
• Infection studies using wild-type and PilA-deficient GBS mutants in a mouse model.
• Assessment of bacterial dissemination, host immune cell infiltration, and blood-brain barrier (BBB) permeability.
• Neutrophil depletion experiments.

Main Results:

• PilA directly binds to collagen, facilitating GBS interaction with the host α₂β₁ integrin.
• This interaction activates host chemokine expression and enhances neutrophil recruitment.
• Mice infected with PilA-deficient GBS showed reduced mortality, decreased neutrophil infiltration, and limited CNS dissemination.
• Neutrophil depletion reduced BBB permeability and GBS penetration into the CNS.

Conclusions:

• GBS PilA adhesin has a dual role in GBS pathogenesis, mediating both immune activation and CNS entry.
• PilA-mediated virulence is dependent on neutrophil influx, highlighting the complex interplay between bacterial factors and host immunity.
• Targeting bacterial pili may offer a novel strategy for preventing GBS CNS infections.