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Title: Efficacy of membrane TNF mediated host resistance is dependent on mycobacterial virulence
Authors: Dambuza, I 
Allie, N 
Fick, L 
Johnston, N 
Fremond, C 
Mitchell, J 
Quesniaux, V. F. J 
Ryffel, B 
Jacobs, M 
Keywords: Tumour necrosis factor;Mycobacterium tuberculosis;Mycobacterium bovis BCG
Issue Date: 2007
Publisher: Elsevier
Source: Dambuza, I., Allie, N., Fick, L. et al. 2007. Efficacy of membrane TNF mediated host resistance is dependent on mycobacterial virulence. Tuberculosis, 88: 221–234. []
Journal: Tuberculosis 
Abstract: TNF is required for protection against virulent and non-virulent mycobacterial infections. Here we compared the effect of Tm-TNF and sTNF, two different molecular forms of TNF, in virulent and non-virulent murine challenge models. Using non-virulent Mycobacterium bovis BCG intranasal infection we established that immunity is durably compromised in Tm-TNF mice, with augmented bacilli burden, leading to chronic but non-lethal infection. Acute infection by a virulent Mycobacterium tuberculosis low-dose aerosol challenge was controlled in Tm-TNF mice with bacilli burdens equivalent to that in WT mice and pulmonary pathology characterised by the formation of well-defined, bactericidal granulomas. Protective immunity was however compromised in Tm-TNF mice during the chronic phase of M. tuberculosis infection, with increased lung bacterial growth and inflammatory cell activation, dissolution of granulomas associated with dispersed iNOS expression, increased pulmonary IFNg and IL-10 expression but decreased IL-12 production, followed by death. In conclusion, membrane TNF is sufficient to control non-virulent, M. bovis BCG infection, and acute but not chronic infection with virulent M. tuberculosis
ISSN: 1472-9792
Appears in Collections:HWSci - Journal Articles (DHET subsidised)

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