Depletion of alveolar macrophages ameliorates virus-induced disease following a pulmonary coronavirus infection.
Depletion of alveolar macrophages ameliorates virus-induced disease following a pulmonary coronavirus infection.
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DOI：
10.1371/journal.pone.0090720
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Varga SM
中科院分区：
文献类型：
--
作者：
Hartwig SM;Holman KM;Varga SM
冠状病毒引起的人类呼吸道疾病可以从轻微到严重。然而，肺部冠状病毒感染的发病机制知之甚少。小鼠肝炎病毒1型（MHV-1）是一种能够在高度易感的C3 H/HeJ小鼠中引起严重发病率和死亡率的第2组冠状病毒。我们先前已经表明，CD 4和CD 8 T细胞在介导MHV-1诱导的疾病中起着关键作用。在这里，我们评估了肺泡巨噬细胞（AM）在调节适应性免疫反应和随后的疾病中的作用。在MHV-1感染前使用氯膦酸盐脂质体消耗AM与MHV-1诱导的发病率和死亡率显著改善相关。AM耗竭导致肺气道中病毒特异性CD 4 T细胞数量减少。此外，在去除AM的小鼠中，在MHV-1感染后观察到肺组织和肺气道中的THBE的频率和总数显著增加。我们的研究结果表明，AM在调节MHV-1诱导的发病率和死亡率中起关键作用。
Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1) is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM) in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality.
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影响因子：
4.4
作者：
Khanolkar, Aaruni;Fulton, Ross B.;Harty, John T.
通讯作者：
Harty, John T.
DOI：
10.4049/jimmunol.1000423
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fulton RB;Meyerholz DK;Varga SM
通讯作者：
Varga SM
影响因子：
5.4
作者：
Khanolkar, Aaruni;Hartwig, Stacey M.;Varga, Steven M.
通讯作者：
Varga, Steven M.
影响因子：
3.7
作者：
Rivera, Rachel;Hutchens, Martha;Luker, Gary D.
通讯作者：
Luker, Gary D.
影响因子：
5.4
作者：
Khanolkar, Aaruni;Hartwig, Stacey M.;Harty, John T.
通讯作者：
Harty, John T.