Murine alveolar macrophages limit replication of vaccinia virus
Murine alveolar macrophages limit replication of vaccinia virus
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DOI：
10.1016/j.virol.2007.01.033
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发表时间：
2007-06-20
期刊：
影响因子：
3.7
通讯作者：
Luker, Gary D.
中科院分区：
文献类型：
--
作者：
Rivera, Rachel;Hutchens, Martha;Luker, Gary D.
由于对猴痘向人类的人畜共患传播和正痘病毒造成的生物恐怖主义威胁的担忧，人们对探索宿主防御这些病原体的细胞和分子机制重新产生了兴趣。特别是，必须了解呼吸道中的病毒-宿主相互作用，这是天花的感染途径，也是猴痘的可能传播途径。在这项研究中，我们分析了肺泡巨噬细胞在痘病毒感染中的功能，使用表达萤火虫荧光素酶的重组牛痘病毒来量化小鼠和细胞培养中的感染。用脂质体氯膦酸盐消耗肺泡巨噬细胞可降低小鼠感染的总体严重程度，包括通过生物发光成像确定的牛痘的更大复制和全身传播。在牛痘感染期间，肺泡巨噬细胞的缺乏增加了肺中粒细胞和粒细胞/单核细胞祖细胞的总数，这表明肺泡巨噬细胞的保护作用可能部分通过减少宿主炎症来介导。肺泡巨噬细胞还限制呼吸道上皮中的牛痘感染，如来自肺泡巨噬细胞和肺上皮的细胞系的共培养模型所示。总的来说，这些数据表明，肺泡巨噬细胞是宿主防御痘病毒局部和全身感染的关键决定因素。(C)2007年爱思唯尔公司All rights reserved.
Because of concerns about zoonotic transmission of monkeypox to humans and the bioterrorism threat posed by orthopoxviruses, there is renewed interest in probing cellular and molecular mechanisms of host defense to these pathogens. In particular, it is essential to understand viral-host interactions in the respiratory tract, which is the route of infection for smallpox and a likely route of transmission for monkeypox. In this study, we analyze functions of alveolar macrophages in poxvirus infection, using a recombinant vaccinia virus expressing firefly luciferase to quantify infection in mice and cell culture. Depletion of alveolar macrophages with liposomal clodronate worsens the overall severity of infection in mice, including greater replication and systemic dissemination of vaccinia as determined by bioluminescence imaging. Absence of alveolar macrophages increases total numbers of granulocytes and granulocytes/monocyte progenitor cells in the lungs during vaccinia infection, indicating that protective effects of alveolar macrophages may be mediated in part by reducing the host inflammation. Alveolar macrophages also limit vaccinia infection in respiratory epithelium, as shown by a co-culture model of cell lines derived from alveolar macropbages and lung epithelium. Collectively, these data demonstrate that alveolar macrophages are key determinants of host defense against local and systemic infection with poxviruses. (C) 2007 Elsevier Inc. All rights reserved.