Efficacy of membrane TNF mediated host resistance is dependent on mycobacterial virulence
Efficacy of membrane TNF mediated host resistance is dependent on mycobacterial virulence
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DOI：
10.1016/j.tube.2007.08.011
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发表时间：
2008-05-01
期刊：
影响因子：
3.2
通讯作者：
Jacobs, M.
中科院分区：
文献类型：
--
作者：
Dambuza, I.;Allie, N.;Jacobs, M.
TNF是抵抗毒性和非毒性分枝杆菌感染所必需的。在这里，我们比较了Tm-TNF和sTNF，TNF的两种不同分子形式，在毒性和非毒性小鼠攻击模型的效果。使用无毒力的牛分枝杆菌BCG鼻内感染，我们建立了免疫力持久受损的Tm-TNF小鼠，增加杆菌负荷，导致慢性但非致死性感染。在Tm-TNF小鼠中控制了毒性结核分枝杆菌两剂量气溶胶激发的急性感染，其杆菌负荷与WT小鼠相当，肺部病理学特征为形成明确的杀菌性肉芽肿。然而，在M的慢性期，Tm-TNF小鼠的保护性免疫受到损害。肺结核感染，肺细菌生长和炎性细胞活化增加，与分散的iNOS表达相关的肉芽肿溶解，肺IFN γ和IL-10表达增加，但IL-12产生减少，随后死亡。总之，膜TNF足以控制无毒力M。牛BCG感染，急性而非慢性感染强毒M。结核(C)2007爱思唯尔有限公司保留所有权利。
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 tow-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 IFN gamma 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. (C) 2007 Elsevier Ltd. All rights reserved.