A cell biologist connects her research to bacterial brain invasion.
My main interest is in understanding how some cells organize their structure and components asymmetrically — a property called cell polarity. When I moved to my current job in a medical faculty I was asked to teach a course on infectious diseases. So I was very excited by the publication of a paper from Mathieu Coureuil at the University of Paris Descartes and his colleagues that brings together my passion and my teaching activity. The work shows that a bacterial pathogen can reach the brain by destroying cell polarity (Coureuil, M. et al. Science325, 83–87; 2009).
Few bacteria are able to cross the blood–brain barrier, and it is not known whether those that can do so by moving through or between cells. The bacterium Neisseria meningitidis can cross this barrier. It adheres to cells lining the brain's blood vessels using type IV pili — hairlike appendages that connect the bacterium to the interior of these endothelial cells.
Using human brain endothelial cells and N. meningitidis in culture, Coureuil et al. show that a complex of polarity proteins — Cdc42, PAR6, PKC and PAR3, which form tight junctions between endothelial cells — are recruited to the site of bacterial adhesion. This results in depletion of these proteins at the junctions and thus the formation of gaps between infected cells.
Although this study was performed in cultured cells owing to a lack of suitable animal models, it strongly suggests that N. meningitidis enters the brain by disrupting the junctions between cells — allowing the bacteria to squeeze in between them — and not by penetrating the cells themselves.
This elegant paper unveils a route that may also be used by other pathogens that cross the blood–brain barrier. It also underscores an important function of cell polarity: protecting our brain from infectious diseases.
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Gotta, M. Journal club. Nature 463, 139 (2010). https://doi.org/10.1038/463139f