Reactivation of latent tuberculosis infection in TNF-deficient mice
Reactivation of latent tuberculosis infection in TNF-deficient mice
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DOI：
10.4049/jimmunol.171.6.3110
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发表时间：
2003-09-15
影响因子：
4.4
通讯作者：
Ryffel, B
中科院分区：
文献类型：
--
作者：
Botha, T;Ryffel, B
TNF缺陷小鼠对结核分枝杆菌H37 Rv感染高度易感。在这里，我们问是否TNF是所需的感染后免疫气溶胶感染的小鼠。感染后2周开始的4周化疗将CFU降低至检测不到的水平。虽然野生型小鼠的CFU略有上升，但停止化疗后感染得到控制，但TNF缺陷型小鼠在肺、脾和肝中出现感染再激活，细菌负荷高，在13-18周内致命。TNF缺陷小鼠的易感性增加伴随着T细胞和巨噬细胞进入肺的募集和活化减少，有缺陷的肉芽肿形成和诱导型NO合酶表达减少。肺中趋化因子的产生减少可能解释了T细胞的次优募集和活化以及不受控制的感染。因此，尽管化疗大大减少了分枝杆菌的负荷，但TNF缺陷小鼠无法补偿和建立保护性免疫应答。总之，内源性TNF是维持潜伏性结核感染的关键，在其缺乏时，不会产生特异性免疫。免疫学杂志，2003年。
TNF-deficient mice are highly susceptible to Mycobacterium tuberculosis H37Rv infection. Here we asked whether TNF is required for postinfectious immunity in aerosol-infected mice. Chemotherapy for 4 wk commencing 2 wk postinfection reduced CFU to undetectable levels. While wild-type mice had a slight rise in CFU, but controlled infection upon cessation of chemotherapy, TNF-deficient mice developed reactivation of infection with high bacterial loads in lungs, spleen, and liver, which was fatal within 13-18 wk. The increased susceptibility of TNF-deficient mice was accompanied by diminished recruitment and activation of T cells and macrophages into the lung, with defective granuloma, formation and reduced inducible NO synthase expression. Reduced chemokine production in the lung might explain suboptimal recruitment and activation of T cells and uncontrolled infection. Therefore, despite a massive reduction of the mycobacterial load by chemotherapy, TNF-deficient mice were unable to compensate and mount a protective immune response. In conclusion, endogenous TNF is critical to maintain latent tuberculosis infection, and in its absence no specific immunity is generated. The Journal of Immunology, 2003.