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

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dc.contributor.authorDambuza, Ivyen_ZA
dc.contributor.authorKeeton, Roanneen_ZA
dc.contributor.authorAllie, Nasiemaen_ZA
dc.contributor.authorHsu, Nai-Jenen_ZA
dc.contributor.authorRandall, Philippaen_ZA
dc.contributor.authorSebesho, Boipeloen_ZA
dc.contributor.authorFick, Lizetteen_ZA
dc.contributor.authorQuesniaux, Valerie J Fen_ZA
dc.contributor.authorJacobs, Muazzamen_ZA
dc.date.accessioned2015-11-23T12:35:16Z
dc.date.available2015-11-23T12:35:16Z
dc.date.issued2011en_ZA
dc.description.abstractOf 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.identifier.apacitationDambuza, 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/11427/15320en_ZA
dc.identifier.chicagocitationDambuza, 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/11427/15320en_ZA
dc.identifier.citationDambuza, 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.0025121en_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
dc.identifier.urihttp://hdl.handle.net/11427/15320
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0025121
dc.identifier.vancouvercitationDambuza 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.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2011 Dambuza et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherGranulomasen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherMouse modelsen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherRoot structureen_ZA
dc.subject.otherCytokinesen_ZA
dc.titleReactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor miceen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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