Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase.
Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase.
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DOI：
10.1084/jem.194.8.1123
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发表时间：
2001-10-15
期刊：
影响因子：
--
通讯作者：
Nathan C
中科院分区：
文献类型：
--
作者：
Ehrt S;Schnappinger D;Bekiranov S;Drenkow J;Shi S;Gingeras TR;Gaasterland T;Schoolnik G;Nathan C
巨噬细胞活化决定结核杆菌（Mtb）感染的结果。干扰素-γ（IFN-γ）通过驱动Janus酪氨酸激酶（JAK）/信号转导和转录激活因子依赖性转录诱导和PKR依赖性翻译抑制来激活巨噬细胞。这里报道的基于微阵列的实验放大了这一图景。暴露于IFN-γ和/或Mtb导致巨噬细胞中25%的监测基因组的表达改变。IFN-γ抑制的基因数量超过了诱导的基因数量，并且大部分抑制是转录的。与免疫和炎症相关的基因被诱导的数量是被抑制的五倍。Mtb与IFN-γ的作用类似或协同多于拮抗。非活结核分枝杆菌或聚苯乙烯珠的吞噬作用影响许多基因，但活结核分枝杆菌感染的巨噬细胞的转录特征是不同的。涉及缺乏诱导型一氧化氮合酶和/或吞噬细胞氧化酶的巨噬细胞的研究表明，这两种抗微生物酶有助于协调巨噬细胞活化的深刻转录重塑。
Macrophage activation determines the outcome of infection by Mycobacterium tuberculosis (Mtb). Interferon-γ (IFN-γ) activates macrophages by driving Janus tyrosine kinase (JAK)/signal transducer and activator of transcription–dependent induction of transcription and PKR-dependent suppression of translation. Microarray-based experiments reported here enlarge this picture. Exposure to IFN-γ and/or Mtb led to altered expression of 25% of the monitored genome in macrophages. The number of genes suppressed by IFN-γ exceeded the number of genes induced, and much of the suppression was transcriptional. Five times as many genes related to immunity and inflammation were induced than suppressed. Mtb mimicked or synergized with IFN-γ more than antagonized its actions. Phagocytosis of nonviable Mtb or polystyrene beads affected many genes, but the transcriptional signature of macrophages infected with viable Mtb was distinct. Studies involving macrophages deficient in inducible nitric oxide synthase and/or phagocyte oxidase revealed that these two antimicrobial enzymes help orchestrate the profound transcriptional remodeling that underlies macrophage activation.
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影响因子：
56.9
作者：
Diefenbach, A;Schindler, H;Bogdan, C
通讯作者：
Bogdan, C
影响因子：
4.8
作者：
Godon, C;Lagniel, G;Labarre, J
通讯作者：
Labarre, J
影响因子：
4.8
作者：
Bae, YS;Sung, JY;Rhee, SG
通讯作者：
Rhee, SG
DOI：
10.1073/pnas.091110098
发表时间：
2001-05-08
影响因子：
11.1
作者：
Detweiler, CS;Cunanan, DB;Falkow, S
通讯作者：
Falkow, S
影响因子：
30.8
作者：
Cho, RJ;Huang, MX;Lockhart, DJ
通讯作者：
Lockhart, DJ