Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice

 

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dc.contributor.author Dambuza, Ivy en_ZA
dc.contributor.author Keeton, Roanne en_ZA
dc.contributor.author Allie, Nasiema en_ZA
dc.contributor.author Hsu, Nai-Jen en_ZA
dc.contributor.author Randall, Philippa en_ZA
dc.contributor.author Sebesho, Boipelo en_ZA
dc.contributor.author Fick, Lizette en_ZA
dc.contributor.author Quesniaux, Valerie J F en_ZA
dc.contributor.author Jacobs, Muazzam en_ZA
dc.date.accessioned 2015-11-23T12:35:16Z
dc.date.available 2015-11-23T12:35:16Z
dc.date.issued 2011 en_ZA
dc.identifier.citation Dambuza, I., Keeton, R., Allie, N., Hsu, N. J., Randall, P., Sebesho, B., ... & Jacobs, M. (2010). Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice. PloS one, 6(11), e25121-e25121. doi:10.1371/journal.pone.0025121 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15320
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0025121
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, IFNγ 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_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Mycobacterium tuberculosis en_ZA
dc.subject.other Granulomas en_ZA
dc.subject.other Inflammation en_ZA
dc.subject.other Tuberculosis en_ZA
dc.subject.other Mouse models en_ZA
dc.subject.other Macrophages en_ZA
dc.subject.other Root structure en_ZA
dc.subject.other Cytokines en_ZA
dc.title Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2011 Dambuza et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Immunology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Dambuza, I., Keeton, R., Allie, N., Hsu, N., Randall, P., Sebesho, B., ... Jacobs, M. (2011). Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice. <i>PLoS One</i>, http://hdl.handle.net/11427/15320 en_ZA
dc.identifier.chicagocitation Dambuza, Ivy, Roanne Keeton, Nasiema Allie, Nai-Jen Hsu, Philippa Randall, Boipelo Sebesho, Lizette Fick, Valerie J F Quesniaux, and Muazzam Jacobs "Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/15320 en_ZA
dc.identifier.vancouvercitation Dambuza I, Keeton R, Allie N, Hsu N, Randall P, Sebesho B, et al. Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice. PLoS One. 2011; http://hdl.handle.net/11427/15320. en_ZA
dc.identifier.ris TY - Journal Article AU - Dambuza, Ivy AU - Keeton, Roanne AU - Allie, Nasiema AU - Hsu, Nai-Jen AU - Randall, Philippa AU - Sebesho, Boipelo AU - Fick, Lizette AU - Quesniaux, Valerie J F AU - Jacobs, Muazzam AB - 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, IFNγ 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. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0025121 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice TI - Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice UR - http://hdl.handle.net/11427/15320 ER - en_ZA


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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.