Mice lacking both TNF and IL-1 receptors exhibit reduced lung inflammation and delay in onset of death following infection with a highly virulent H5N1 virus.
Mice lacking both TNF and IL-1 receptors exhibit reduced lung inflammation and delay in onset of death following infection with a highly virulent H5N1 virus.
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DOI：
10.1086/656365
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发表时间：
2010-10-15
期刊：
影响因子：
--
通讯作者：
Tumpey TM
中科院分区：
文献类型：
--
作者：
Perrone LA;Szretter KJ;Katz JM;Mizgerd JP;Tumpey TM
H5 N1亚型的高致病性禽流感病毒继续跨越物种屏障感染人类并引起严重疾病。已经表明，过度的免疫应答有助于哺乳动物中H5 N1病毒感染的发病机制。特别是，H5 N1病毒感染与促炎细胞因子的高表达相关，包括白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）。我们通过使用三种信号受体TNF-R1、TNF-R2和IL-1-RI缺陷的三重突变（TM）小鼠，研究了两种细胞因子对H5 N1病毒疾病结局的复合影响。TM小鼠表现出降低的发病率和死亡率的致命攻击后，致命的H5 N1病毒的死亡率显着延迟，而没有观察到这样的差异与毒性较低的A/PR/8/34（H1N1）病毒。感染H5 N1的TM小鼠显示肺组织中细胞因子产生减少，感染后肺中巨噬细胞和嗜中性粒细胞数量减少。此外，气道切片的形态测定分析显示，与感染野生型小鼠相比，感染H5 N1的TM小鼠的炎症范围较窄。来自TNF或IL-1受体的组合信号促进最大的肺部炎症，这可能导致H5 N1病毒感染引起的疾病的严重性。
Highly pathogenic avian influenza viruses of the H5N1 subtype continue to cross the species barrier to infect humans and cause severe disease. It has been suggested that an exaggerated immune response contributes to the pathogenesis of H5N1 virus infection in mammals. In particular, H5N1 virus infections are associated with a high expression of the proinflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor- alpha (TNF-α). We investigated the compounding affects of both cytokines on the outcome of H5N1 virus disease by using triple mutant (TM) mice deficient in three signaling receptors, TNF-R1, TNF-R2, and IL-1-RI. TM mice exhibited reduced morbidity and a significant delay in mortality following lethal challenge with a lethal H5N1 virus, whereas no such differences were observed with the less virulent A/PR/8/34 (H1N1) virus. H5N1 infected TM mice displayed diminished cytokine production in lung tissue and a quantifiable decline of macrophages and neutrophils in the lungs post-infection. Moreover, morphometric analysis of airway sections revealed less extensive inflammation in H5N1-infected TM mice compared with infected wild type mice. The combined signaling from the TNF or IL-1 receptors promotes maximal lung inflammation that may contribute to the severity of disease caused by H5N1 virus infection.
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影响因子：
168.9
作者：
Claas, ECJ;Osterhaus, ADME;Webster, RG
通讯作者：
Webster, RG
影响因子：
5.8
作者：
Lucas, Rudolf;Verin, Alexander D.;Black, Stephen M.;Catravas, John D.
通讯作者：
Catravas, John D.
DOI：
10.1152/ajplung.00353.2003
发表时间：
2004-06-01
影响因子：
4.9
作者：
Mizgerd, JP;Lupa, MM;Silverman, ES
通讯作者：
Silverman, ES
影响因子：
3.1
作者：
Kobayashi, Yoshiro
通讯作者：
Kobayashi, Yoshiro
DOI：
10.1016/s0140-6736(04)15595-5
发表时间：
2004-02-21
期刊：
Lancet (London, England)
影响因子：
--
作者：
Peiris JS;Yu WC;Leung CW;Cheung CY;Ng WF;Nicholls JM;Ng TK;Chan KH;Lai ST;Lim WL;Yuen KY;Guan Y
通讯作者：
Guan Y