Respiratory infection promotes T cell infiltration and amyloid-β deposition in APP/PS1 mice
Respiratory infection promotes T cell infiltration and amyloid-β deposition in APP/PS1 mice
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DOI：
10.1016/j.neurobiolaging.2013.07.025
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Lynch, Marina A.
中科院分区：
文献类型：
--
作者：
McManus, Roisin M.;Higgins, Sarah C.;Lynch, Marina A.
阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，其特征是淀粉样蛋白沉积和神经原纤维缠结。有人认为炎症变化与疾病有关；然而，尚不清楚这些是否是持续神经退行性变的结果，或者炎症本身是否导致疾病发病机制。最近的研究表明，接触感染会加速AD患者的认知能力下降，并且在AD大脑中检测到了病原体。然而，感染对神经炎症和病理学的影响仍然知之甚少。在这项研究中，我们研究了外周感染对 APP/PS1 小鼠 AD 病理学的影响。我们发现，感染革兰氏阴性呼吸道病原体百日咳博德特氏菌后 8 周，老年 APP/PS1 小鼠中产生 IFN γ 和 IL-17 的 T 细胞和 NKT 细胞显着浸润。这伴随着神经胶质活化和淀粉样蛋白-b 沉积的增加。数据表明，感染是 AD 进展的关键因素，强调了老年人感染早期诊断和治疗的重要性。 (c) 2014 Elsevier Inc. 保留所有权利。
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by deposits of amyloid-beta and neurofibrillary tangles. It has been suggested that inflammatory changes are associated with disease; however, it has not been established whether these are a consequence of ongoing neurodegeneration or whether inflammation itself contributes to disease pathogenesis. Recent studies suggest that exposure to infection can accelerate cognitive decline in AD patients, and pathogens have been detected in the AD brain. However, the influence of infection on neuroinflammation and pathology remains poorly understood. In this study, we examined the effect of a peripheral infection on AD pathology in APP/PS1 mice. We found that, 8 weeks after infection with the Gram negative respiratory pathogen Bordetella pertussis, there was significant infiltration of IFN gamma- and IL-17-producing T cells and NKT cells in older APP/PS1 mice. This was accompanied by increased glial activation and amyloid-b deposition. The data suggest that infection is a critical factor in the progression of AD, emphasising the importance of early diagnosis and treatment of infections in elderly individuals. (c) 2014 Elsevier Inc. All rights reserved.