The pathogenesis of tuberculous meningitis

Abstract

Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury. Here we review the steps from primary infection to cerebral disease, factors that contribute to the virulence of the organism and the vulnerability of the host and discuss the immune response and the clinical manifestations arising. Priorities for future research directions are suggested. K E Y W O R D S mycobacterial, endothelial cells, granulocytes, microglia cells, monocytes/macrophages, myeloid cells, neutrophils, T Lymphocytes, Th17 cells at the site of infection activates macrophages and DCs to produce cytokines and antimicrobial factors that contribute to containment of the TB bacillus. 2 This inflammatory process results in the formation of a granuloma, which encapsulates the infected cells and retards the replication of TB bacilli and can lead to latent infection. However, in

Tumor necrosis factor antagonists for paradoxical inflammatory reactions in the central nervous system tuberculosis

“…Inflammation is believed to be enhanced by the exposure of excess M. tuberculosis antigens to the immune system during anti-TB therapy, which in turn would cause a disproportionate response and its clinical expression in form of PR. [ 23 , 24 ] In HIV co-infected patients, starting antiretroviral therapy will trigger this response in a patient receiving TB treatment. It is entirely plausible that amplification of the inflammatory response takes place in most patients, if not all, and that PR/IRIS represents an extreme of this clinical expression.…”

Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics

“…Dissemination to the central nervous system Understanding of the microbial and immune processes that allow M. tuberculosis to disseminate from the respiratory epithelium to reach the meninges remains incomplete 2,4 . The foundations of what is known were laid through natural history and autopsy studies in the pre-chemotherapy era.…”

“…The majority of TBM pathology is believed to result from the host inflammatory response; 2 several pro-and anti-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL) 1β, IL-6, IL-8, and IL-10 are induced in TBM 11,12 . Disequilibrium of pro-and anti-inflammatory cytokines influence the severity and course of TBM, Figure 1 2,13 .…”

“…In this article we review important recently published studies that have informed our current understanding of TBM pathogenesis and diagnostics. We do not seek to present a comprehensive review of the history of TBM pathogenesis and diagnostics as a number of detailed papers that have addressed this recently [1][2][3] . Rather we provide a commentary of key studies published within the last 5 years and summarise knowledge gaps and future considerations to enable progress in the field.…”

Progress and history of the 10th Federation of African Immunological Societies Congress

“…This issue of JLB features a number of manuscripts describing these infectious diseases, including data on the impact of maternal HIV‐exposure, feeding status, and the microbiome on infant cellular immunity, as reported by Clive Gray and colleages . The pathogenesis of tuberculous meningitis is described by Robert Wilkinson and Benabdessalem and their colleagues and shows how granzyme B induced by Rv0140 antigen in latently infected individuals with tuberculosis is different from those with active tuberculosis. The challenges associated with treating Buruli Ulcer are investigated by Sammy Aboagye and colleages and, in an experimental model, Frank Brombacher and his colleagues highlight the contribution of IL‐4Rα‐expressing CD11c + cells in driving optimal cellular responses during Schistosoma mansoni infection in mice.…”