Transgenic mice enriched in omega-3 fatty acids are more susceptible to pulmonary tuberculosis: impaired resistance to tuberculosis in fat-1 mice.
Transgenic mice enriched in omega-3 fatty acids are more susceptible to pulmonary tuberculosis: impaired resistance to tuberculosis in fat-1 mice.
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DOI：
10.1086/650344
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发表时间：
2010-02-01
期刊：
影响因子：
--
通讯作者：
McMurray DN
中科院分区：
文献类型：
--
作者：
Bonilla DL;Fan YY;Chapkin RS;McMurray DN
除了它们的健康益处之外，膳食ω-3脂肪酸（n-3 PUFA）可以削弱宿主对细胞内病原体的抵抗力。以前，我们和其他人已经表明，n-3 PUFA处理的巨噬细胞在体外控制结核分枝杆菌感染很差。野生型和fat-1转基因小鼠用强毒H37 Rv M感染。肺结核通过气溶胶途径。我们评估了肺的细菌学和组织病理学变化，以及原代巨噬细胞体外活化和抗分枝杆菌能力的差异。fat-1小鼠更容易感染结核病，这一点可以从肺部的细菌负荷更高和炎症反应更弱得到证明。从fat-1小鼠获得的巨噬细胞更容易感染M.与野生型巨噬细胞相比，这损害了fat-1小鼠细胞中的细菌控制，与促炎细胞因子分泌减少、氧化代谢受损和M.结核菌-噬菌体共定位。我们发现，内源性生产的n-3多不饱和脂肪酸在脂肪-1小鼠增加了他们对结核病的易感性，这可以部分解释为减少激活和抗分枝杆菌反应的细胞从脂肪-1小鼠。这些数据表明，补充n-3 PUFA的饮食可能对M.结核病，并引起对人体omega-3膳食补充剂安全性的关注。
Besides their health benefits, dietary omega-3 fatty acids (n-3 PUFAs) can impair host resistance to intracellular pathogens. Previously, we and others have showed that n-3 PUFA–treated macrophages poorly control Mycobacterium tuberculosis infection in vitro. Wild-type and fat-1 transgenic mice were infected with virulent H37Rv M. tuberculosis via the aerosol route. We evaluated bacteriological and histopathological changes in lungs, as well as differences in activation and antimycobacterial capacity in primary macrophages ex vivo. fat-1 mice were more susceptible to tuberculosis, as demonstrated by higher bacterial loads and less robust inflammatory responses in lungs. Macrophages obtained from fat-1 mice were more readily infected with M. tuberculosis in vitro, compared with wild-type macrophages. This impaired bacterial control in cells from fat-1 mice correlated with reduced proinflammatory cytokine secretion, impaired oxidative metabolism, and diminished M. tuberculosis–lysotracker colocalization within phagosomes. We showed that endogenous production of n-3 PUFAs in fat-1 mice increases their susceptibility to tuberculosis, which could be explained in part by diminished activation and antimycobacterial responses in cells from fat-1 mice. These data suggest that n-3 PUFA–supplemented diets might have a detrimental effect on immunity to M. tuberculosis and raise concerns regarding the safety of omega-3 dietary supplementation in humans.
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影响因子：
7.1
作者：
BANG, HO;DYERBERG, J;SINCLAIR, HM
通讯作者：
SINCLAIR, HM
DOI：
10.1073/pnas.0334211100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Bagga, D;Wang, L;Reddy, ST
通讯作者：
Reddy, ST
影响因子：
6
作者：
Fritsche, KL;Shahbazian, LM;Berg, JN
通讯作者：
Berg, JN
影响因子：
8.8
作者：
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通讯作者：
Karlstad, MD
影响因子：
4.9
作者：
Changsen, C;Franzblau, SG;Palittapongarnpim, P
通讯作者：
Palittapongarnpim, P