Haemophilus influenzae outer membrane vesicle-induced blood-brain barrier permeability during experimental meningitis

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.