title: Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood-brain barrier.
abstract: Neisseria meningitidis is a commensal bacterium of the human nasopharynx. Occasionally, this bacterium reaches the bloodstream and causes meningitis after crossing the blood-brain barrier by an unknown mechanism. An immunohistological study of a meningococcal sepsis case revealed that neisserial adhesion was restricted to capillaries located in low blood flow regions in the infected organs. This study led to the hypothesis that drag forces encountered by the meningococcus in the bloodstream determine its attachment site in vessels. We therefore investigated the ability of N. meningitidis to bind to endothelial cells in the presence of liquid flow mimicking the bloodstream with a laminar flow chamber. Strikingly, average blood flows reported for various organs strongly inhibited initial adhesion. As cerebral microcirculation is known to be highly heterogeneous, cerebral blood velocity was investigated at the level of individual vessels using intravital imaging of rat brain. In agreement with the histological study, shear stress levels compatible with meningococcal adhesion were only observed in capillaries, which exhibited transient reductions in flow. The flow chamber assay revealed that, after initial attachment, bacteria resisted high blood velocities and even multiplied, forming microcolonies resembling those observed in the septicemia case. These results argue that the combined mechanical properties of neisserial adhesion and blood microcirculation target meningococci to transiently underperfused cerebral capillaries and thus determine disease development.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U570, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mairey
authors.forename: Auguste
authors.initials: A
authors.lastname: Genovesio
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Donnadieu
authors.forename: Christine
authors.initials: C
authors.lastname: Bernard
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pinard
authors.forename: Jacques
authors.initials: J
authors.lastname: Seylaz
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Olivo-Marin
authors.forename: Xavier
authors.initials: X
authors.lastname: Nassif
authors.forename: Guillaume
authors.initials: G
authors.lastname: Duménil
mesh_terms: D000818:Animals; D001287:Attachment Sites, Microbiological / Q000502:physiology*; D001422:Bacterial Adhesion; D001812:Blood-Brain Barrier / Q000166:cytology / Q000382:microbiology* / Q000473:pathology; D002196:Capillaries / Q000382:microbiology; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D042783:Endothelial Cells / Q000166:cytology; D004780:Environment, Controlled; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006801:Humans; D007223:Infant; D008585:Meningitis, Meningococcal / Q000473:pathology; D008833:Microcirculation; D009345:Neisseria meningitidis / Q000166:cytology / Q000502:physiology*; D051381:Rats; D012039:Regional Blood Flow; D012772:Shock, Septic / Q000473:pathology; D013314:Stress, Mechanical