FimH, a TLR4 ligand, induces innate antiviral responses in the lung leading to protection against lethal influenza infection in mice
FimH, a TLR4 ligand, induces innate antiviral responses in the lung leading to protection against lethal influenza infection in mice
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DOI：
10.1016/j.antiviral.2011.09.004
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发表时间：
2011-11-01
影响因子：
7.6
通讯作者：
Ashkar, Ali A.
中科院分区：
文献类型：
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作者：
Abdul-Careem, Mohamed F.;Mian, M. Firoz;Ashkar, Ali A.
菌毛H蛋白(FimH)是一种新的TLR4配体，已被证明能刺激天然免疫系统，并引起对细菌和病毒感染的保护性反应。在这里，我们在小鼠模型中评估了局部注射FimH对甲型流感感染的保护作用。我们发现，在甲型流感病毒致死攻击之前，鼻腔注射FimH可以降低野生型小鼠的发病率和死亡率，但不能降低TLR4(-/-)小鼠的死亡率。重要的是。与TLR4(-/-)小鼠相比，FimH能够减少肺内早期的病毒负荷，导致最少的细胞渗透到气道腔，并减轻野生型小鼠感染后的肺部病理。预防性地将FimH局部注射给C57BL/6小鼠，而不是TLR4(-/-)小鼠，可增加IL-12和RANTES反应以及中性粒细胞在气道腔内的募集。这些影响与流感感染的病程有关。FimH介导的抗流感病毒反应似乎部分依赖于肺泡巨噬细胞。FimH的抗病毒作用可能是通过先天介质(TNF-α、IL-12或RANTES)和/或通过激活反馈抑制环来抑制肺部炎症，可能是FimH介导的保护作用的潜在机制。因此，FIMH有望成为控制流感病毒感染的一种可能的预防性手段。(C)2011爱思唯尔B.V.保留所有权利。
Fimbriae H protein (FimH) is a novel TLR4 ligand that has been shown to stimulate the innate immune system and elicits protective responses against bacterial and viral infections. Here, we evaluated the protective role of local delivery of FimH against influenza A infection in a mouse model. We show that intranasal delivery of FimH prior to lethal challenge with influenza A virus, resulted in decreased morbidity and mortality in wild-type, but not TLR4(-/-), mice. Importantly. FimH was able to reduce the early viral burden in the lung leading to minimal cell infiltration into the airway lumen and reduced pulmonary pathology following infection in wild type mice compared to TLR4(-/-) mice. Local delivery of FimH to C57BL/6, not TLR4(-/-), mice in a prophylactic manner increased the IL-12 and RANTES responses as well as neutrophil recruitment into the airway lumen. These effects correlate to the course of influenza infection. The FimH-mediated antiviral response against influenza virus appears to be partially dependent on alveolar macrophages. The antiviral effects are likely mediated by the innate mediators (TNF-alpha, IL-12 or RANTES) and/or by activation of a feedback inhibition loop to curtail the pulmonary inflammation possibly be the potential mechanisms involved in FimH-mediated protection. FimH thus holds promise to be a possible prophylactic mean of control against influenza viral infection. (C) 2011 Elsevier B.V. All rights reserved.