TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis

International Conference on Cytopathology

August 31-September 02, 2015 Toronto, Canada

Ngiambudulu Mbandu Francisco

University of Cape Town, South Africa

Posters-Accepted Abstracts: J Cytol Histol

Abstract :

Tuberculosis of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumor necrosis factor (TNF) plays a critical role in the initial and longterm host immune protection against Mycobacterium tuberculosis, which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF in the control of cerebral Mycobacterium tuberculosis infection and its protective immune responses in the CNS were not clear. We generated neuron-specific TNF-deficient (NsTNF�/�) mice and compared outcomes of disease against TNFf/f control and global TNF�/� mice. Mycobacterial burden in brains, lungs and spleens were compared and cerebral pathology and cellular contributions analyzed by microscopy and flow cytometry after Mycobacterium tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). Intracerebral Mycobacterium tuberculosis infection of TNF�/� mice rendered animals highly susceptible accompanied by uncontrolled intra- and extra-cellular bacilli replication and eventual mortality. In contrast, NsTNF�/� mice were resistant to infection and presented with a phenotype similar to that in TNFf/f control mice. Impaired immunity in TNF�/� mice was associated with altered genes synthesis in the brain and characterized by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. Our data demonstrate that neuron-derived TNF has a limited role in immune responses but overall TNF production is necessary for protective immunity against CNS-TB.

Biography :

Email: franciscongiamb@gmail.com