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Reactivation of M. tuberculosis Infection in Trans- Membrane Tumour Necrosis Factor Mice

Show simple item record Dambuza, Ivy Keeton, Roanne Allie, Nasiema Hsu, Nai-Jen Randall, Philippa Sebesho, Boipelo Fick, Lizette Quesniaux, Valerie J. F. Jacobs, Muazzam
dc.contributor.editor Ryffel, Bernhard 2017-08-24T09:37:01Z 2017-08-24T09:37:01Z 2011 2017-08 2011
dc.identifier.citation Dambuza, I. et al. 2011 'Reactivation of M. tuberculosis Infection in Trans-Membrane Tumour Necrosis Factor Mice' PLoS ONE 6(11): e25121. doi:10.1371/journal.pone.0025121 en_US
dc.description.abstract Of those individuals who are infected with M. tuberculosis, 90% do not develop active disease and represents a large reservoir of M. tuberculosis with the potential for reactivation of infection. Sustained TNF expression is required for containment of persistent infection and TNF neutralization leads to tuberculosis reactivation. In this study, we investigated the contribution of soluble TNF (solTNF) and transmembrane TNF (Tm-TNF) in immune responses generated against reactivating tuberculosis. In a chemotherapy induced tuberculosis reactivation model, mice were challenged by aerosol inhalation infection with low dose M. tuberculosis for three weeks to establish infection followed chemotherapeutic treatment for six weeks, after which therapy was terminated and tuberculosis reactivation investigated. We demonstrate that complete absence of TNF results in host susceptibility to M. tuberculosis reactivation in the presence of established mycobacteria-specific adaptive immunity with mice displaying unrestricted bacilli growth and diffused granuloma structures compared to WT control mice. Interestingly, bacterial re-emergence is contained in Tm-TNF mice during the initial phases of tuberculosis reactivation, indicating that Tm-TNF sustains immune pressure as in WT mice. However, Tm-TNF mice show susceptibility to long term M. tuberculosis reactivation associated with uncontrolled influx of leukocytes in the lungs and reduced IL-12p70, IFNc and IL-10, enlarged granuloma structures, and failure to contain mycobacterial replication relative to WT mice. In conclusion, we demonstrate that both solTNF and Tm-TNF are required for maintaining immune pressure to contain reactivating M. tuberculosis bacilli even after mycobacteria-specific immunity has been established. en_US
dc.description.sponsorship South African National Research Foundation (NRF) en_US
dc.format.extent 10 p. en_US
dc.format.medium PDF en_US
dc.language.iso en en_US
dc.publisher PLoS ONE en_US
dc.relation.requires Adobe acrobat reader en_US
dc.subject M. tuberculosis infection en_US
dc.subject Tumour necrosis factor mice en_US
dc.title Reactivation of M. tuberculosis Infection in Trans- Membrane Tumour Necrosis Factor Mice en_US
dc.type Article en_US
dc.rights.holder National Research Foundation en_US

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