Membrane TNF confers protection to acute mycobacterial infection

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dc.contributor.authorFremond, Cecileen_ZA
dc.contributor.authorAllie, Nasiemaen_ZA
dc.contributor.authorDambuza, Ivy Men_ZA
dc.contributor.authorGrivennikov, Sergeien_ZA
dc.contributor.authorYeremeev, Vladimiren_ZA
dc.contributor.authorQuesniaux, Valerieen_ZA
dc.contributor.authorJacobs, Muazzamen_ZA
dc.contributor.authorRyffel, Bernharden_ZA
dc.date.accessioned2015-10-12T10:57:31Z
dc.date.available2015-10-12T10:57:31Z
dc.date.issued2005en_ZA
dc.description.abstractBACKGROUND:Tumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF). METHODS: C57BL/6, TNF KO and mem-TNF mice were infected with M. tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice. RESULTS: While TNF-KO mice succumbed to infection within 4-5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acute Mtb infection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO mice. CONCLUSION: Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute Mtb infection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF.en_ZA
dc.identifier.apacitationFremond, C., Allie, N., Dambuza, I. M., Grivennikov, S., Yeremeev, V., Quesniaux, V., ... Ryffel, B. (2005). Membrane TNF confers protection to acute mycobacterial infection. <i>Respiratory Research</i>, http://hdl.handle.net/11427/14195en_ZA
dc.identifier.chicagocitationFremond, Cecile, Nasiema Allie, Ivy M Dambuza, Sergei Grivennikov, Vladimir Yeremeev, Valerie Quesniaux, Muazzam Jacobs, and Bernhard Ryffel "Membrane TNF confers protection to acute mycobacterial infection." <i>Respiratory Research</i> (2005) http://hdl.handle.net/11427/14195en_ZA
dc.identifier.citationFremond, C.; et al. (2005). Membrane TNF confers protection to acute mycobacterial infection. Respiratory Research, 6: 136. DOI:10.1186/1465-9921-6-136en_ZA
dc.identifier.ris TY - Journal Article AU - Fremond, Cecile AU - Allie, Nasiema AU - Dambuza, Ivy M AU - Grivennikov, Sergei AU - Yeremeev, Vladimir AU - Quesniaux, Valerie AU - Jacobs, Muazzam AU - Ryffel, Bernhard AB - BACKGROUND:Tumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF). METHODS: C57BL/6, TNF KO and mem-TNF mice were infected with M. tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice. RESULTS: While TNF-KO mice succumbed to infection within 4-5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acute Mtb infection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO mice. CONCLUSION: Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute Mtb infection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF. DA - 2005 DB - OpenUCT DO - 10.1186/1465-9921-6-136 DP - University of Cape Town J1 - Respiratory Research LK - https://open.uct.ac.za PB - University of Cape Town PY - 2005 T1 - Membrane TNF confers protection to acute mycobacterial infection TI - Membrane TNF confers protection to acute mycobacterial infection UR - http://hdl.handle.net/11427/14195 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14195
dc.identifier.urihttp://dx.doi.org/10.1186/1465-9921-6-136
dc.identifier.vancouvercitationFremond C, Allie N, Dambuza IM, Grivennikov S, Yeremeev V, Quesniaux V, et al. Membrane TNF confers protection to acute mycobacterial infection. Respiratory Research. 2005; http://hdl.handle.net/11427/14195.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_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 Licenseen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceRespiratory Researchen_ZA
dc.source.urihttp://www.respiratory-research.com/en_ZA
dc.subject.otherMycobacterium tuberculosis H37Rven_ZA
dc.subject.othermembrane TNFen_ZA
dc.subject.otherTNF-deficiencyen_ZA
dc.subject.otherT cell recruitmenten_ZA
dc.subject.othergranulomaen_ZA
dc.titleMembrane TNF confers protection to acute mycobacterial infectionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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