Early Changes by 18Fluorodeoxyglucose Positron Emission Tomography Coregistered with Computed Tomography Predict Outcome after Mycobacterium tuberculosis Infection in Cynomolgus Macaques
Early Changes by 18Fluorodeoxyglucose Positron Emission Tomography Coregistered with Computed Tomography Predict Outcome after Mycobacterium tuberculosis Infection in Cynomolgus Macaques
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DOI：
10.1128/iai.01599-13
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发表时间：
2014-06-01
影响因子：
3.1
通讯作者：
Lin, Philana Ling
中科院分区：
文献类型：
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作者：
Coleman, M. Teresa;Maiello, Pauline;Lin, Philana Ling
感染低剂量结核分枝杆菌的食蟹猴发生与人类相似的活动性结核和潜伏性感染，这为研究临床上无症状的感染早期事件提供了机会。（18）氟脱氧葡萄糖放射性示踪剂与正电子发射断层扫描和计算机断层扫描（FDG PET/CT）共配准提供了测量疾病进展的非侵入性方法。我们试图确定肉芽肿演变的时间模式，区分活动性疾病和潜在的结果。猕猴（n=10）感染低剂量M。感染期间进行FDG PET/CT检查。在感染后24周，动物被分类为具有活动性疾病（n=3）或潜伏性感染（n=6），其中一只“潜伏”猴。成像特性（例如，病变数量、代谢活性、大小、矿化和病变分布）在活动组和潜伏组之间进行比较。早在感染后3周，在后来发展为活动性疾病的动物中观察到的肺肉芽肿多于那些发展为潜伏性感染的动物。随着时间的推移，在活动性疾病动物中出现新的病变，但在潜伏性动物中没有。活动性疾病动物而非潜伏期动物的肉芽肿和纵隔淋巴结在早期时间点的代谢活性持续增加。在潜伏感染的动物中，3周时存在较少的病变并且缺乏新的病变发展，这表明先天性和快速适应性反应对于预防活动性结核病至关重要。在新的疫苗策略中，应更加强调先天性反应和/或适应性反应的快速招募，特别是在气道中。
Cynomolgus macaques infected with low-dose Mycobacterium tuberculosis develop both active tuberculosis and latent infection similar to those of humans, providing an opportunity to study the clinically silent early events in infection. (18)Fluorodeoxyglucose radiotracer with positron emission tomography coregistered with computed tomography (FDG PET/CT) provides a noninvasive method to measure disease progression. We sought to determine temporal patterns of granuloma evolution that distinguished active-disease and latent outcomes. Macaques (n=10) were infected with low-dose M. tuberculosis with FDG PET/CT performed during infection. At 24 weeks postinfection, animals were classified as having active disease (n=3) or latent infection (n=6), with one "percolator" monkey. Imaging characteristics (e.g., lesion number, metabolic activity, size, mineralization, and distribution of lesions) were compared among active and latent groups. As early as 3 weeks postinfection, more pulmonary granulomas were observed in animals that would later develop active disease than in those that would develop latent infection. Over time, new lesions developed in active-disease animals but not in latent animals. Granulomas and mediastinal lymph nodes from active-disease but not latent animals consistently increased in metabolic activity at early time points. The presence of fewer lesions at 3 weeks and the lack of new lesion development in animals with latent infection suggest that innate and rapid adaptive responses are critical to preventing active tuberculosis. A greater emphasis on innate responses and/or rapid recruitment of adaptive responses, especially in the airway, should be emphasized in newer vaccine strategies.