Lack of the pattern recognition molecule mannose-binding lectin increases susceptibility to influenza A virus infection.
Lack of the pattern recognition molecule mannose-binding lectin increases susceptibility to influenza A virus infection.
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DOI：
10.1186/1471-2172-11-64
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发表时间：
2010-12-23
期刊：
影响因子：
3
通讯作者：
Takahashi K
中科院分区：
文献类型：
--
作者：
Chang WC;White MR;Moyo P;McClear S;Thiel S;Hartshorn KL;Takahashi K
甘露糖结合凝集素(MBL)是一种模式识别的天然免疫分子，在体外抑制甲型流感病毒感染。在人类中，由于基因多态性导致的MBL缺陷与感染易感性有关。在动物模型研究中，缺乏MBL的小鼠对包括单纯疱疹病毒2型在内的某些病原体易感，这些临床观察得到了证实。我们证明了MBL存在于幼稚健康的野生型(WT)小鼠的肺中，并且MBL缺失的小鼠更容易受到IAV感染。给予重组人MBL(RhMBL)可逆转感染表型，证实感染敏感性是由MBL介导的。MBL的抗病毒机制包括激活凝集素补体途径和凝血，需要血清因子。在感染后第1天，WT组小鼠肺中的白细胞(WBC)高于MBL缺失组。相比之下，肺组织中的巨噬细胞(MΦS)的凋亡率是WT小鼠的两倍。此外，MBL缺陷的巨噬细胞在体外似乎对凋亡敏感。最后，在IAV感染期间，与肺损伤相关的可溶性因子在MBL缺失小鼠的肺中增加。这些结果表明MBL在抗IAV感染中起着关键作用。MBL在清除IAV和维持肺内环境稳定方面起着关键作用。此外，我们的研究结果还提示MBL缺乏可能是IAV感染的一个危险因素，MBL可能是IAV感染的一种有用的辅助治疗。
Mannose-binding lectin (MBL), a pattern recognition innate immune molecule, inhibits influenza A virus infection in vitro. MBL deficiency due to gene polymorphism in humans has been associated with infection susceptibility. These clinical observations were confirmed by animal model studies, in which mice genetically lacking MBL were susceptible to certain pathogens, including herpes simplex virus 2. We demonstrate that MBL is present in the lung of naïve healthy wild type (WT) mice and that MBL null mice are more susceptible to IAV infection. Administration of recombinant human MBL (rhMBL) reverses the infection phenotype, confirming that the infection susceptibility is MBL-mediated. The anti-viral mechanisms of MBL include activation of the lectin complement pathway and coagulation, requiring serum factors. White blood cells (WBCs) in the lung increase in WT mice compared with MBL null mice on day 1 post-infection. In contrast, apoptotic macrophages (MΦs) are two-fold higher in the lung of MBL null mice compared with WT mice. Furthermore, MBL deficient macrophages appear to be susceptible to apoptosis in vitro. Lastly, soluble factors, which are associated with lung injury, are increased in the lungs of MBL null mice during IAV infection. These results suggest that MBL plays a key role against IAV infection. MBL plays a key role in clearing IAV and maintaining lung homeostasis. In addition, our findings also suggest that MBL deficiency maybe a risk factor in IAV infection and MBL may be a useful adjunctive therapy for IAV infection.
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