Bacterial Meningitis: The Role of Transforming Growth Factor-Beta in Innate Immunity and Secondary Brain Damage

Project 6 of the NCCR ‘Neural Plasticity and Repair’ focuses on mechanisms of immunity and tissue damage in autoimmune and infectious diseases of the central nervous system (CNS). In one of the subprojects, the influence of transforming growth factor-β (TGF-β) on the immune reactivity of the CNS was investigated. In mice with Streptococcus pneumoniae-induced meningitis, a deletion of TGF-β receptor II on leukocytes is found to enhance recruitment of neutrophils to the site of infection and to promote bacterial clearance. The improved host defense against S. pneumoniae was associated with an almost complete prevention of meningitis-induced vasculitis, a major intracranial complication leading to brain damage. The data show that endogenous TGF-β suppresses host defense against bacterial infection in the CNS. This contrasts with findings from other body compartments that suggested that TGF-β is a powerful chemotactic cytokine and increases microbial clearance.