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Haemophilus influenzae outer membrane vesicle-induced blood-brain barrier permeability during experimental meningitis
B Wispelwey1, E J Hansen, W M Scheld
1Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Abstract:
Haemophilus influenzae type b (Hib) lipopolysaccharide (LPS) may be present in the cerebrospinal fluid largely as part of outer membrane vesicles (OMV), which could possibly alter its activity. Similar to inoculation of purified Hib LPS, intracisternal inoculation of Hib OMV into adult rats resulted in dose- and time-dependent increases in blood-brain barrier permeability. Polymyxin B, but not an oligosaccharide-specific monoclonal antibody, significantly inhibited the activity of Hib OMV. No change in blood-brain barrier permeability occurred in leukopenic rats inoculated with Hib OMV. Hib OMV was as active as purified Hib LPS on a weight basis and therefore appears to be a relevant vehicle for the delivery of LPS during meningitis.
Insights
Haemophilus influenzae type b (Hib) outer membrane vesicles (OMV) increase blood-brain barrier permeability, similar to purified Hib lipopolysaccharide (LPS). Polymyxin B neutralized Hib OMV activity, suggesting LPS within OMV is key to meningitis pathogenesis.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Haemophilus influenzae type b (Hib) lipopolysaccharide (LPS) is implicated in meningitis.
- LPS may be delivered via outer membrane vesicles (OMV) in cerebrospinal fluid, potentially affecting its activity.
Purpose of the Study:
- To investigate the role of Hib OMV in altering blood-brain barrier (BBB) permeability.
- To compare the activity of Hib OMV with purified Hib LPS.
Main Methods:
- Intracisternal inoculation of Hib OMV and purified Hib LPS into adult rats.
- Administration of Polymyxin B or a monoclonal antibody to assess OMV activity.
- Evaluation of BBB permeability in leukopenic rats.
Main Results:
- Hib OMV inoculation caused dose- and time-dependent increases in BBB permeability, similar to purified Hib LPS.
- Polymyxin B significantly inhibited Hib OMV activity, while the monoclonal antibody did not.
- No BBB permeability changes were observed in leukopenic rats.
Conclusions:
- Hib OMV is an active vehicle for LPS delivery, contributing to BBB disruption during meningitis.
- The LPS component within OMV is responsible for its effect on BBB permeability.