Mannose-binding lectin contributes to deleterious inflammatory response in pandemic H1N1 and avian H9N2 infection.

Mannose-binding lectin contributes to deleterious inflammatory response in pandemic H1N1 and avian H9N2 infection.
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DOI:
10.1093/infdis/jir691
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发表时间:
2012-01-01
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Lau YL
Lau YL
中科院分区:
其他
文献类型:
--
作者:
Ling MT;Tu W;Han Y;Mao H;Chong WP;Guan J;Liu M;Lam KT;Law HK;Peiris JS;Takahashi K;Lau YL

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背景: 甘露糖结合凝集素(MBL)是一种模式识别分子,是宿主防御的第一道防线。大流行性H1N1(PdmH1N1)甲型流感病毒在2009年造成大规模感染,目前在全球范围内传播。禽流感H9N2(H9N2/G1)病毒已经感染了人类,有可能成为下一次大流行病毒。MBL在pdmH1N1和H9N2/G1病毒感染中的抗病毒作用和免疫调节作用尚未被研究。方法:在这项研究中,使用 野生型(WT)和MBL基因敲除(KO)小鼠模型来检测MBL在pdmH1N1和H9N2/G1病毒感染中的作用。结果: 我们的研究表明,在体外,MBL与pdmH1N1和H9N2/G1病毒结合,可能是通过MBL的碳水化合物识别结构域。野生型小鼠发生了更严重的疾病,在流感病毒感染期间,体重减轻幅度比MBL KO小鼠更大。此外,与MBL KO小鼠相比,MBL WT小鼠的促炎细胞因子和趋化因子的产生增加,这表明MBL可以上调炎症反应,这可能会加剧pdmH1N1和H9N2/G1病毒感染。结论: 我们的研究首次提供了体内证据,表明MBL可能是pdmH1N1和H9N2/G1感染过程中的一个危险因素,因为它上调了促炎反应。
Background. Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. Methods. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Results. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Conclusions. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.
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发表时间: 2000-10-01
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