Antibody directed against mannan of the Mycobacterium tuberculosis cell envelope provokes blood-brain barrier breakdown

Previous studies demonstrated that blood-brain barrier (BBB) breakdown obse rved at the cerebral level during experimental allergic encephalomyelitis ( EAE) arises from the presence of Mycobacterium tuberculosis in Freund's adj uvant and not only from the encephalitogenic antigens. The main objective o f this study was to check if the mannan moiety of lipoarabinomannan present in the mycobacterial cell envelope is responsible for an immune response p rovoking a BBB breakdown. The results showed that: firstly, the complete Fr eund's adjuvant (CFA) contains a high release of polysaccharides; secondly, the rats immunized with the CFA present important serum concentration of a nti-mannan antibody; and finally, a single 2-mg dose of anti-mannan antibod y injected intravenously in naive rats provokes an immediate and reversible BBB breakdown. These results suggest that mannan arising from the solubili zation of the mycobacterial cell wall in Freund's adjuvant induces a high p roduction of anti-mannan antibody, which, in turn, provokes a BBB breakdown and possibly facilitates the induction of EAE. (C) 2000 Published by Elsev ier Science B.V. All rights reserved.