The role of cell type-specific tumour necrosis factor in protective immunity against neurotuberculosis
type: CreativeWork
description: Neurotuberculosis is the most severe form of extra-pulmonary tuberculosis, characterised by the formation of rich foci a brain form of granulomas, and tuberculous meningitis. Granulomas contain mycobacteria by recruitment of immune cells that surround the bacteria. The cytokine tumour necrosis factor has been found to be involved in the recruitment of the immune cells and structure maintenance of granulomas. Tumour necrosis factor is a multifunctional proinflammatory cytokine which play a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) infection. This cytokine is synthesised by several cell types of hematopoetic origin, such as microglia/macrophages, neutrophils, dendritic cells and lymphocytes, and non-hematopoetic origin such as astrocytes and neurons. During neurotuberculosis, excess of tumour necrosis factor has been implicated in persisting hyperinflammation, however, deficiency of tumour necrosis factor lead to uncontrolled bacterial growth; both phenomena causing necrotic lysis. Thus, a need exists to investigate the contribution of tumour necrosis factor by specific cell types in the control of cerebral M. tuberculosis infection and its protective immune response. In this study, we investigated the role of tumour necrosis factor derived from neurons, microglia/macrophages, neutrophils, CD4+ and CD8+ T cells in host immunity against M. tuberculosis; using an experimental murine model with cell type-specific gene targeting. We found that mice deficient for tumour necrosis factor in neurons (NsTNF-/-), as well as from microglia/macrophages and neutrophils (M-TNF-/-) are not susceptible to M. tuberculosis infection with a phenotype similar to wild type mice. Interestingly, mice with ablation of tumour necrosis factor in myeloid (microglia/macrophages, neutrophils) and CD4+ and CD8+ T cells (MTTNF-/-) were highly susceptible to M. tuberculosis infection with a phenotype similar to that of comp…
abstract: Neurotuberculosis is the most severe form of extra-pulmonary tuberculosis, characterised by the formation of rich foci a brain form of granulomas, and tuberculous meningitis. Granulomas contain mycobacteria by recruitment of immune cells that surround the bacteria. The cytokine tumour necrosis factor has been found to be involved in the recruitment of the immune cells and structure maintenance of granulomas. Tumour necrosis factor is a multifunctional proinflammatory cytokine which play a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) infection. This cytokine is synthesised by several cell types of hematopoetic origin, such as microglia/macrophages, neutrophils, dendritic cells and lymphocytes, and non-hematopoetic origin such as astrocytes and neurons. During neurotuberculosis, excess of tumour necrosis factor has been implicated in persisting hyperinflammation, however, deficiency of tumour necrosis factor lead to uncontrolled bacterial growth; both phenomena causing necrotic lysis. Thus, a need exists to investigate the contribution of tumour necrosis factor by specific cell types in the control of cerebral M. tuberculosis infection and its protective immune response. In this study, we investigated the role of tumour necrosis factor derived from neurons, microglia/macrophages, neutrophils, CD4+ and CD8+ T cells in host immunity against M. tuberculosis; using an experimental murine model with cell type-specific gene targeting. We found that mice deficient for tumour necrosis factor in neurons (NsTNF-/-), as well as from microglia/macrophages and neutrophils (M-TNF-/-) are not susceptible to M. tuberculosis infection with a phenotype similar to wild type mice. Interestingly, mice with ablation of tumour necrosis factor in myeloid (microglia/macrophages, neutrophils) and CD4+ and CD8+ T cells (MTTNF-/-) were highly susceptible to M. tuberculosis infection with a phenotype similar to that of comp…
author: Francisco, Ngiambudulu Mbandu
language: eng
date published: 2013
date modified: 2026-07-22T22:23:45Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Division of Immunology

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11427/8706