Dorman Susan E, Hatem Christine L, Tyagi Sandeep, Aird Katherine, Lopez-Molina Javier, Pitt M Louise M, Zook Bernard C, Dannenberg Arthur M, Bishai William R, Manabe Yukari C
Department of Medicine, School of Medicine, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, USA.
Infect Immun. 2004 Mar;72(3):1700-5. doi: 10.1128/IAI.72.3.1700-1705.2004.
The rabbit model of tuberculosis (TB) is important because rabbits develop a disease that is similar to TB in humans, namely, granulomas with caseous necrosis, liquefaction, and cavities. We describe here a comparison of inbred and outbred New Zealand White rabbits infected by aerosol with either Mycobacterium tuberculosis Erdman or H37Rv strain. Five weeks after infection with either bacillary strain, the inbred rabbits had significantly larger pulmonary tubercles than did outbred rabbits (2.7 versus 1.4 mm in diameter; P < 0.01). After infection with H37Rv, the inbred rabbits had significantly more pulmonary tubercles than did the outbred rabbits (98 +/- 12 versus 33 +/- 13; P < 0.01), with more mycobacterial CFU per tubercle (809 +/- 210 versus 215 +/- 115; P = 0.027) (means +/- standard errors of the means). Compared with histologic examination of lung granulomas from outbred rabbits, histologic examination of those from inbred rabbits showed more caseous necrosis, more visible bacilli, and fewer mature epithelioid cells. The delayed-type hypersensitivity (DTH) responses to intradermal tuberculin were significantly lower, and peritoneal macrophages from uninfected inbred rabbits produced significantly less tumor necrosis factor alpha after lipopolysaccharide (LPS) stimulation in vitro than those from the outbred rabbits (2,413 +/- 1,154 versus 8,879 +/- 966 pg/ml). We conclude that these inbred rabbits were more susceptible to TB than their outbred counterparts and had an impaired ability to contain disease, resulting in more grossly visible tubercles that were larger than those observed in outbred rabbits. Preliminary evidence is presented for a cell-mediated immune defect with lower DTH responses and macrophages that have a decreased ability to respond to in vitro stimulation with LPS or M. tuberculosis infection.
结核病（TB）的兔模型很重要，因为兔子会患上一种与人类结核病相似的疾病，即具有干酪样坏死、液化和空洞的肉芽肿。我们在此描述了近交系和远交系新西兰白兔经气溶胶感染结核分枝杆菌埃尔德曼株或H37Rv株后的比较。在用任一菌株感染5周后，近交系兔子的肺部结核结节明显大于远交系兔子（直径分别为2.7毫米和1.4毫米；P < 0.01）。在用H37Rv感染后，近交系兔子的肺部结核结节明显多于远交系兔子（98±12个对33±13个；P < 0.01），每个结核结节中的分枝杆菌菌落形成单位（CFU）更多（809±210个对215±115个；P = 0.027）（均值±均值的标准误）。与远交系兔子肺部肉芽肿的组织学检查相比，近交系兔子的组织学检查显示干酪样坏死更多、可见杆菌更多且成熟上皮样细胞更少。对皮内结核菌素的迟发型超敏反应（DTH）明显更低，未感染的近交系兔子的腹膜巨噬细胞在体外经脂多糖（LPS）刺激后产生的肿瘤坏死因子α明显少于远交系兔子（2413±1154皮克/毫升对8879±966皮克/毫升）。我们得出结论，这些近交系兔子比它们的远交系同类对结核病更易感，且控制疾病的能力受损，导致出现比远交系兔子中观察到的更大且肉眼更易见的结核结节。初步证据表明存在细胞介导的免疫缺陷，DTH反应较低，且巨噬细胞对LPS体外刺激或结核分枝杆菌感染的反应能力下降。
