NOD2 controls the nature of the inflammatory response and subsequent fate of Mycobacterium tuberculosis and M. bovis BCG in human macrophages.
NOD2 controls the nature of the inflammatory response and subsequent fate of Mycobacterium tuberculosis and M. bovis BCG in human macrophages.
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NOD2控制着人类巨噬细胞中结核分枝杆菌和BCG的炎症反应的性质和随后的命运。
DOI：
10.1111/j.1462-5822.2010.01544.x
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发表时间：
2011-03
影响因子：
3.4
通讯作者：
Schlesinger LS
中科院分区：
文献类型：
--
作者：
Brooks MN;Rajaram MV;Azad AK;Amer AO;Valdivia-Arenas MA;Park JH;Núñez G;Schlesinger LS
结核分枝杆菌（Mycobacterium tuberculosis，M.tb）是一种适应宿主的巨噬细胞内病原体，引起结核病。巨噬细胞中的细胞内模式识别受体如核苷酸结合寡聚化结构域（NOD）蛋白调节促炎细胞因子的产生。NOD 2介导的信号通路响应结核分枝杆菌已主要在小鼠模型和细胞系中进行了研究，但没有在原代人巨噬细胞中。因此，我们试图确定NOD 2在调节细胞因子的产生和毒性结核分枝杆菌和减毒牛分枝杆菌BCG（BCG）在人巨噬细胞中的生长中的作用。我们检测了单核细胞分化过程中NOD 2的表达，并观察到培养2-3天后NOD 2转录物和蛋白质的显著增加。用NOD 2配体胞壁酰二肽预处理人单核细胞衍生的和肺泡巨噬细胞，以RIP 2依赖性方式增强了对结核分枝杆菌和BCG的应答中TNF-α和IL-1β的产生。NOD 2介导的细胞因子反应显着减少后敲低NOD 2表达，通过使用小干扰RNA（siRNA）在人类巨噬细胞。最后，NOD 2控制结核分枝杆菌和BCG在人巨噬细胞中的生长，而仅控制BCG在鼠巨噬细胞中的生长。总之，我们的研究结果提供了证据，NOD 2是一个重要的细胞内受体在调节宿主的结核分枝杆菌和卡介苗感染的人巨噬细胞的反应。
Mycobacterium tuberculosis (M.tb), which causes tuberculosis, is a host-adapted intracellular pathogen of macrophages. Intracellular pattern recognition receptors in macrophages such as nucleotide-binding oligomerization domain (NOD) proteins regulate pro-inflammatory cytokine production. NOD2-mediated signalling pathways in response to M.tb have been studied primarily in mouse models and cell lines but not in primary human macrophages. Thus we sought to determine the role of NOD2 in regulating cytokine production and growth of virulent M.tb and attenuated Mycobacterium bovis BCG (BCG) in human macrophages. We examined NOD2 expression during monocyte differentiation and observed a marked increase in NOD2 transcript and protein following 2–3 days in culture. Pre-treatment of human monocyte-derived and alveolar macrophages with the NOD2 ligand muramyl dipeptide enhanced production of TNF-α and IL-1β in response to M.tb and BCG in a RIP2-dependent fashion. The NOD2-mediated cytokine response was significantly reduced following knock-down of NOD2 expression by using small interfering RNA (siRNA) in human macrophages. Finally, NOD2 controlled the growth of both M.tb and BCG in human macrophages, whereas controlling only BCG growth in murine macrophages. Together, our results provide evidence that NOD2 is an important intracellular receptor in regulating the host response to M.tb and BCG infection in human macrophages.
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影响因子：
4.8
作者：
Gutierrez, O;Pipaon, C;Fernandez-Luna, JL
通讯作者：
Fernandez-Luna, JL
DOI：
10.1073/pnas.0504271103
发表时间：
2006-01-03
影响因子：
11.1
作者：
Gavrilin, MA;Bouakl, IJ;Wewers, MD
通讯作者：
Wewers, MD
影响因子：
4.4
作者：
Henning, Lisa N.;Azad, Abul K.;Schlesinger, Larry S.
通讯作者：
Schlesinger, Larry S.
影响因子：
7.8
作者：
Barnich, N;Aguirre, JE;Podolsky, DK
通讯作者：
Podolsky, DK
影响因子：
4.4
作者：
Beharka, AA;Gaynor, CD;Schlesinger, LS
通讯作者：
Schlesinger, LS