Disseminated and rapidly fatal tuberculosis in mice bearing a defective allele at IFN regulatory factor 8.
Disseminated and rapidly fatal tuberculosis in mice bearing a defective allele at IFN regulatory factor 8.
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DOI：
10.4049/jimmunol.0800680
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发表时间：
2009-03-01
期刊：
影响因子：
--
通讯作者：
Gros P
中科院分区：
文献类型：
--
作者：
Marquis JF;LaCourse R;Ryan L;North RJ;Gros P
IRF（干扰素调节因子）家族成员IRF-8参与含有基因启动子的ISRE（干扰素刺激反应元件）或GAS（γ干扰素激活位点）元件的转录激活，以响应IFN-γ。为了测试IRF-8在宿主防御结核病中的作用，携带缺陷IRF-8 R294 C等位基因的BXH-2小鼠通过静脉内和气溶胶途径用低剂量的毒性结核分枝杆菌进行攻击。BXH-2小鼠对M.肺结核的发病率很高，表现为脾、肝和肺中微生物的快速和不受控制的复制，导致非常早的死亡。BXH-2缺陷在非常早期（感染后10天）表达为表达Nos 2的肺巨噬细胞中不受控制的细胞内病原体复制、受损的肉芽肿形成、感染向远处部位的快速传播以及感染组织的快速坏死。在感染BXH-2的肺中完全不存在IL-12 p40诱导，IFN-γ产生严重减少，并且T细胞引发受损，突出了IRF-8在该过程中的关键作用。总的来说，这些结果将IRF-8确定为宿主防御结核病的关键调节剂。
The IRF (Interferon Regulatory Factor) family member IRF-8 participates in transcriptional activation of ISRE (Interferon Stimulated Response Element) or GAS (Gamma interferon Activation Site) elements containing gene promotors, in response to IFN-γ. To test the role of IRF-8 in host defenses against tuberculosis, BXH-2 mice which bear a defective IRF-8R294C allele, were challenged with low-doses of virulent Mycobacterium tuberculosis via the intravenous and aerosol routes. BXH-2 mice were found to be extremely susceptible to M. tuberculosis, as demonstrated by rapid and uncontrolled microbial replication in spleen, liver and lungs leading to very early death. The BXH-2 defect was expressed very early (10 days post-infection) as uncontrolled intracellular pathogen replication in Nos2 expressing lung macrophages, impaired granuloma formation, rapid dissemination of the infection to distant sites, and rapid necrosis of infected tissues. There was complete absence of IL-12p40 induction, severely reduced IFN-γ production, and impaired T cell priming in the lungs of infected BXH-2, highlighting the critical role of IRF-8 in this process. Collectively, these results identify IRF-8 as a critical regulator of host defenses against TB.
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影响因子：
5.4
作者：
BEDIGIAN, HG;SHEPEL, LA;HOPPE, PC
通讯作者：
HOPPE, PC
影响因子：
5.8
作者：
Kawakami, K;Kinjo, Y;Saito, A
通讯作者：
Saito, A
T细胞亚群在小鼠中的肺结核感染的免疫和免疫病理学中的相对重要性。
影响因子：
15.3
作者：
Mogues, T;Goodrich, M E;Ryan, L;LaCourse, R;North, R J
通讯作者：
North, R J
DOI：
10.1073/pnas.1031727100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Mitsos, LM;Cardon, LR;Gros, P
通讯作者：
Gros, P
干扰素伽马在抗性结核病感染中的重要作用。
影响因子：
15.3
作者：
Flynn, J L;Chan, J;Triebold, K J;Dalton, D K;Stewart, T A;Bloom, B R
通讯作者：
Bloom, B R