The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome
The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome
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DOI：
10.1016/j.tube.2007.10.006
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发表时间：
2008-05-01
期刊：
影响因子：
3.2
通讯作者：
Mendez, Susana
中科院分区：
文献类型：
--
作者：
Manabe, Yukari C.;Kesavan, Anup K.;Mendez, Susana
人类潜伏性结核病 (TB) 的大量储存有助于病原体结核分枝杆菌 (Mtb) 在全球的成功。我们试图测试携带 Mtb H37Rv 的兔子气溶胶感染是否可以模拟少杆菌人类潜伏性结核病。肺部感染负担在气溶胶感染后 5 周达到峰值，随后所有兔子都实现了宿主感染遏制。感染后 36 周，三分之一的兔子至少出现一处带有可培养杆菌的干酪肉芽肿，表明持续性少杆菌感染。疾病遏制后开始的皮质类固醇诱导的免疫抑制导致疾病重新激活。百分之七十二的兔子的右上肺叶匀浆中含有可培养的杆菌，而未经治疗的对照组则没有。停用地塞米松可导致淋巴系统恢复，部分兔子出现多中心大干酪样肉芽肿。免疫重建炎症综合征（IRIS）的发展和严重程度取决于免疫抑制时的抗原负荷以及皮质类固醇诱导的免疫抑制期间随后的细菌复制。临床上，许多方面与严重免疫抑制的 HIV 感染患者的 IRIS 相似，这些患者在有效（高活性）抗逆转录病毒治疗后 T 细胞功能恢复。这种皮质类固醇模型是 IRIS 唯一的动物模型。对结核病潜伏期、再激活和 IRIS 的兔模型的进一步研究可能对于理解这些不良模型状态的免疫发病机制以及改进疾病特定阶段的诊断很重要。 (C) 2007 Elsevier Ltd. 保留所有权利。
The large reservoir of human latent tuberculosis (TB) contributes to the global success of the pathogen, Mycobacterium tuberculosis (Mtb). We sought to test whether aerosol infection of rabbits with Mtb H37Rv could model paucibacillary human latent TB. The lung burden of infection peaked at 5 weeks after aerosol infection followed by host containment of infection that was achieved in all rabbits. One-third of rabbits had at least one caseous granuloma with culturable bacilli at 36 weeks after infection suggesting persistent paucibacillary infection. Corticosteroid-induced immunosuppression initiated after disease containment resulted in reactivation of disease. Seventy-two percent of rabbits had culturable bacilli in the right upper lung lobe homogenates compared to none of the untreated controls. Discontinuation of dexamethasone led to predictable lymphoid recovery, with a proportion of rabbits developing multicentric large caseous granuloma. The development and severity of the immune reconstitution inflammatory syndrome (IRIS) was dependent on the antigen load at the time of immunosuppression and subsequent bacillary replication during corticosteroid-induced immunosuppression. Clinically, many aspects were similar to IRIS in severely immunosuppressed HIV-infected patients who have functional restoration of T cells in response to effective (highly active) antiretroviral therapy. This corticosteroid model is the only animal model of the IRIS. Further study of the rabbit model of TB latency, reactivation and IRIS may be important in understanding the immunopathogenesis of these poorly modeled states as well as for improved diagnostics for specific stages of disease. (C) 2007 Elsevier Ltd. All rights reserved.