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Khanyisile Kgoadi

Khanyisile Kgoadi

University of Cape Town, South Africa

Title: Brain dendritic cell recruitment subsequent to Mycobacterium bovis bacillus Calmette-Guerin intracerebral infection contributes to CNS protective immunity

Biography

Biography: Khanyisile Kgoadi

Abstract

Mycobacterium bovis BCG causes inflammation of the CNS referred to as central nervous system tuberculosis (CNS-TB). CNS-TB is a lethal form of tuberculosis that constitutes approximately 5-10% of extra-pulmonary tuberculosis cases. Pathogenesis of CNS-TB is initiated as a secondary infection during haematogenous dissemination of pulmonary infection to the brain parenchyma. CNS-TB is associated with high morbidity and 50% mortality. The mechanisms associated with CNS-TB infection and cells targeted for invasion is mostly unknown. The regulatory role of dendritic cells (DCs) in CNS-TB has been neglected because of their absence during homeostasis. This study investigated DC recruitment kinetics and phenotype in context to CNS-TB. C57BL/6 mice were intracerebrally infected with BCG and sacrificed at different time intervals. Bacterial loads of samples were determined by plating homogenates of organs and counting colony-forming units. Brain DCs were quantified and their phenotype determined using flow cytometry. Bacterial loads showed dissemination of BCG from the brain to the spleen and to a lesser extent to the lungs. A significant increase was observed in the amount of dendritic cells recruited to the brain at week 4 post BCG infections. At week 6, there was a significant drop in the mount of BCG present in the brain. Recruitment of T cells to the brain following BCG infection shows that DCS are successful in presenting antigens to T cells and eliciting an adaptive immune response in CNS-TB. This shows that the CNS is not immune privileged but CNS inflammation caused by mycobacteria is a highly regulated process that limits potential pathology damage.