Accelerated immunopathological response of mice infected with Mycobacterium tuberculosis disrupted in the mce1 operon negative transcriptional regulator
Accelerated immunopathological response of mice infected with Mycobacterium tuberculosis disrupted in the mce1 operon negative transcriptional regulator
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DOI：
10.1111/j.1462-5822.2006.00870.x
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发表时间：
2007-05-01
影响因子：
3.4
通讯作者：
Riley, Lee W.
中科院分区：
文献类型：
--
作者：
Uchida, Yujiro;Casali, Nicola;Riley, Lee W.
结核分枝杆菌引起多种临床结果，由宿主和细菌因素决定。M. MCE 1操纵子中被破坏的结核病导致免疫活性小鼠死亡率增加。该操纵子由mce1R（Rv0165c）负调控。我们研究了mce1R在小鼠感染结果中的作用。在5 x 10（4）尾静脉感染剂量下，感染mce 1 R突变体M的小鼠的中位生存时间（MST）。结核H37Rv感染的小鼠存活时间为293天，而野生型H37Rv感染的小鼠存活时间超过350天（P < 0.0001）。在较高剂量（5 × 10（6））下，mu感染小鼠的MST为32天，而野生型感染小鼠的MST为127天（P < 0.0001）。无论是尾静脉感染还是气溶胶感染，mu感染小鼠的肺部肉芽肿病变都比野生型感染小鼠大。在感染的前4周内，Muximab感染的小鼠无法控制细菌负荷，但即使在后来达到控制后，这些小鼠也死于肉芽肿性肺炎。这些观察结果表明，早期的mce1操纵子产物表达失调决定了后来的肉芽肿组织反应。mce1操纵子可以在体内稳态调节细胞壁结构，从而激发稳态肉芽肿组织反应，允许M.结核病，以建立长期感染。
Mycobacterium tuberculosis causes a variety of clinical outcomes determined by host as well as bacterial factors. M. tuberculosis disrupted in the mce1 operon causes increased mortality in immunocompetent mice. This operon is negatively regulated by mce1R (Rv0165c). We studied the role of mce1R in infection outcome in mice. At 5 x 10(4) tail vein infectious dose, the median survival time (MST) of mice infected with the mce1R mutant M. tuberculosis H37Rv was 293 days, while mice infected with the wild-type H37Rv survived more than 350 days (P < 0.0001). At a higher dose (5 x 10(6)), the MST of mutant-infected mice was 32 days, compared with 127 days for wild type-infected mice (P < 0.0001). With either tail vein or aerosol infection, mutant-infected mice developed larger granulomatous lesions in their lungs than mice infected with the wild type. Mutant-infected mice were unable to control the bacterial burden in the first 4 weeks of infection, but even after achieving control later, these mice succumbed to granulomatous pneumonia. These observations suggest that the early deregulated expression of the mce1 operon products determines later granulomatous tissue response. mce1 operon may homeostatically regulate the cell wall architecture in vivo that elicits a steady-state granuloma tissue response permitting M. tuberculosis to establish a long-term infection.