Establishment of a neonatal rhesus macaque model to study Mycobacterium tuberculosis infection.
Establishment of a neonatal rhesus macaque model to study Mycobacterium tuberculosis infection.
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DOI：
10.1016/s1472-9792(13)70011-8
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Gauduin MC
中科院分区：
文献类型：
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作者：
Cepeda M;Salas M;Folwarczny J;Leandro AC;Hodara VL;de la Garza MA;Dick EJ Jr;Owston M;Armitige LY;Gauduin MC
结核分枝杆菌 (Mtb) 是人类结核病 (TB) 的病原体，估计每年新增 880 万结核病病例和 140 万人死亡。结核病是全世界艾滋病患者死亡的主要原因，但人们对婴儿的早期结核感染或结核病/艾滋病毒合并感染知之甚少。迫切需要一种临床相关的新生动物模型来研究结核病感染。我们已经在新生儿非人灵长类动物 (NHP) 中成功建立了气溶胶新生儿/婴儿模型，该模型模拟了人类新生儿/婴儿中结核分枝杆菌感染的临床和细菌学特征。此外，该模型将允许建立儿童艾滋病的结核病合并感染模型。研究了气溶胶与支气管肺泡内 Mtb 感染的关系。有趣的是，感染后 42 天检测到特定病变，这表明人类儿童中存在典型的戈恩病灶。同时，结核分枝杆菌感染后 4-6 周出现特异性细胞免疫反应。使用酶联免疫斑点 (ELISPOT) 检测，我们发现 IL-12 的产生与常规胸部 X 线照片所见的早期 Mtb 感染病变相关。总体而言，这项工作代表了新生猕猴早期 Mtb 感染的第一个例子。这项研究为我们提供了一个独特的机会来进一步表征免疫发病机制并建立儿童艾滋病的 TB/SIV 混合感染模型。
Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4–6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS.