Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny.
Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny.
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DOI：
10.1084/jem.20172020
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发表时间：
2018-04-02
期刊：
影响因子：
--
通讯作者：
Russell DG
中科院分区：
文献类型：
--
作者：
Huang L;Nazarova EV;Tan S;Liu Y;Russell DG
Huang等人的这项研究表明，不同个体发育的肺巨噬细胞对体内结核分枝杆菌感染的反应不同。肺泡巨噬细胞和间质巨噬细胞采取不同的代谢状态，促进或控制M。结核病的增长，分别。为了了解结核分枝杆菌（Mtb）的感染是如何通过宿主细胞表型调节的，我们表征了在早期感染期间控制或支持细菌生长的宿主吞噬细胞，重点是本体上不同的肺泡巨噬细胞（AM）和间质巨噬细胞（IM）谱系。使用荧光Mtb报告菌株，我们发现，在AM中的杆菌表现出较低的压力和较高的细菌复制比在IM。有趣的是，AM的消耗减少了细菌负荷，而IM的消耗增加了细菌负荷。转录组学分析显示，IM是糖酵解活性，而AM致力于脂肪酸氧化。用糖酵解抑制剂2-脱氧葡萄糖中毒感染的小鼠，减少了IM的数量，但增加了肺中的细菌负荷。此外，在体外巨噬细胞感染，2-脱氧葡萄糖治疗增加细菌的生长，而脂肪酸氧化抑制剂etomoxir抑制细菌的生长。我们假设不同的巨噬细胞谱系对Mtb感染的反应不同，IM表现出营养限制和控制细菌生长，AM代表更营养许可的环境。
This study by Huang et al. demonstrates that lung macrophages of differing ontogeny respond divergently to Mycobacterium tuberculosis infection in vivo. Alveolar macrophages and interstitial macrophages adopt different metabolic states that promote or control M. tuberculosis growth, respectively. To understand how infection by Mycobacterium tuberculosis (Mtb) is modulated by host cell phenotype, we characterized those host phagocytes that controlled or supported bacterial growth during early infection, focusing on the ontologically distinct alveolar macrophage (AM) and interstitial macrophage (IM) lineages. Using fluorescent Mtb reporter strains, we found that bacilli in AM exhibited lower stress and higher bacterial replication than those in IM. Interestingly, depletion of AM reduced bacterial burden, whereas depletion of IM increased bacterial burden. Transcriptomic analysis revealed that IMs were glycolytically active, whereas AMs were committed to fatty acid oxidation. Intoxication of infected mice with the glycolytic inhibitor, 2-deoxyglucose, decreased the number of IMs yet increased the bacterial burden in the lung. Furthermore, in in vitro macrophage infections, 2-deoxyglucose treatment increased bacterial growth, whereas the fatty acid oxidation inhibitor etomoxir constrained bacterial growth. We hypothesize that different macrophage lineages respond divergently to Mtb infection, with IMs exhibiting nutritional restriction and controlling bacterial growth and AMs representing a more nutritionally permissive environment.
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DOI：
10.1084/jem.20140825
发表时间：
2015-05-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goritzka M;Makris S;Kausar F;Durant LR;Pereira C;Kumagai Y;Culley FJ;Mack M;Akira S;Johansson C
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影响因子：
30.3
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30.5
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影响因子：
15.9
作者：
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通讯作者：
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影响因子：
3.2
作者：
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