The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.
Tohoku J Exp Med. 2009 Nov;219(3):257-62. doi: 10.1620/tjem.219.257.
There exists latent tuberculosis, in which small numbers of tubercle bacilli remain viable in the host without visible granulomatous lesions. As few data exist on the mechanisms of latent tuberculosis, it is important to examine latent tuberculosis in terms of pathogenesis and efficacy of chemotherapy. As a first step, we used green fluorescent protein (GFP)-introduced H37Rv Mycobacterium tuberculosis to establish latent tuberculosis in the guinea pig that provides one of the best animal models of tuberculosis. We inoculated the guinea pigs subcutaneously with 100 or 1,000 colony-forming unit (CFU) of tubercle bacilli. During the 300-day follow-up period after infection, there were no clinical signs of disease, suggesting a lack of visible granulomatous lesions. In fact, upon necropsy, no macroscopic tuberculous lesions were recognized, but histopathological examination of the lung, spleen and liver revealed microgranulomas consisting of epithelioid macrophages and lymphocytes without central necrosis. Importantly, photon imaging visualized granulomatous lesions corresponding to these histologically apparent microgranulomas. Tuberculin skin testing of infected guinea pigs showed strong positivity (> or = 10 mm induration) until the end of the experiments. Real-time PCR analysis showed a significant increase in the expression levels of interferon-gamma, tumor necrosis factor-alpha, interleukin-12, and inducible nitric oxide synthase mRNAs in infected lung tissues after 300 days (P < 0.01). As human samples are hardly available to study latent tuberculosis, our guinea pig model would be useful for examining the pathogenesis and molecular mechanisms of latent tuberculosis as well as for monitoring the results of chemotherapy with green fluorescence emission of tubercle bacilli.
存在潜伏性结核，其中少量结核分枝杆菌在宿主中保持存活而没有可见的肉芽肿病变。由于关于潜伏性结核的机制的数据很少，因此从发病机制和化学疗法疗效的角度检查潜伏性结核非常重要。作为第一步，我们使用绿色荧光蛋白（GFP）引入的 H37Rv 结核分枝杆菌在豚鼠中建立潜伏性结核，豚鼠是结核病的最佳动物模型之一。我们将 100 或 1000 个菌落形成单位（CFU）的结核分枝杆菌皮下接种给豚鼠。在感染后的 300 天随访期间，没有疾病的临床症状，表明没有可见的肉芽肿病变。实际上，尸检时未发现肉眼可见的结核病变，但肺，脾和肝的组织病理学检查显示由上皮样巨噬细胞和淋巴细胞组成的微肉芽肿，没有中央坏死。重要的是，光子成像可以可视化与这些组织学上明显的微肉芽肿相对应的肉芽肿性病变。感染豚鼠的结核菌素皮肤试验显示出强阳性（>或= 10 毫米硬结），直到实验结束。实时 PCR 分析显示，感染后 300 天肺组织中干扰素-γ，肿瘤坏死因子-α，白细胞介素-12和诱导型一氧化氮合酶 mRNA 的表达水平显着增加（P <0.01）。由于几乎无法获得人类样本来研究潜伏性结核，因此我们的豚鼠模型将有助于检查潜伏性结核的发病机制和分子机制，并通过结核分枝杆菌的绿色荧光发射监测化学疗法的结果。
