Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice

Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice
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长期饮酒会损害小鼠非特异性和特异性 NK 激活,从而加剧小鼠巨细胞病毒感染

DOI:
10.1096/fba.1019
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发表时间:
2018
期刊:
影响因子:
2.7
通讯作者:
Hui Zhang
Hui Zhang
中科院分区:
--
文献类型:
--
作者:
Alex Little;Yuan;Faya Zhang;Hui Zhang

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长期饮酒会损害免疫系统,从而增加对传染病的易感性。巨细胞病毒感染在人类中很常见,在免疫功能正常的人中通常无症状。然而,它可以在免疫功能低下的个体(如酗酒者)中诱导危及生命的医学并发症。长期饮酒如何加重巨细胞病毒感染尚不清楚。在此,我们使用小鼠巨细胞病毒模型来研究潜在的细胞和分子机制。我们发现,酒精消费增加病毒滴度在脾脏感染后4天,加强体重减轻,抑制脾肿大在感染的急性期。在病毒感染后12小时,饮酒小鼠的IFN-β、脾IFN-γ和产生颗粒酶B的NK细胞的血液水平低于饮水小鼠。此外,酒精消耗减少了感染36小时后产生IL-15的DC,抑制了NK细胞,特别是病毒感染后3 - 6天的Ly 49 H + NK细胞成熟和增殖。令人惊讶的是,饮酒增强了NK细胞和CD 8 + T细胞的持续活化,并增加了颗粒酶B生成细胞。然而,饮酒降低了脾脏和肝脏中穿孔素的表达。总之,长期饮酒通过损害非特异性和特异性NK细胞活化,特别是IFN-γ和穿孔素的产生,加剧了巨细胞病毒感染。
Chronic alcohol consumption increases the susceptibility to infectious diseases by compromising the immune system. Cytomegalovirus infection is common in humans and usually is asymptomatic in immunocompetent people. However, it can induce life‐threatening medical complications in immunocompromised individuals such as alcoholics. How chronic alcohol consumption exacerbates cytomegalovirus infection is not known. Herein, we used a mouse cytomegalovirus model to study the underlying cellular and molecular mechanism. We found that alcohol consumption increased viral titers in spleen after 4 days of infection, enhanced body weight loss and inhibited splenomegaly during the acute phase of infection. Blood level of IFN‐β, splenic IFN‐γ and granzyme B‐producing NK cells were lower in alcohol‐consuming mice than in water‐drinking mice at 12 hours after viral infection. Moreover, alcohol consumption decreased IL‐15‐producing DC after 36 hours infection, inhibited NK cell, specifically Ly49H+ NK cell maturation and proliferation 3‐6 days after viral infection. Surprisingly, alcohol consumption enhanced NK cell and CD8+ T‐cell continuous activation and increased granzyme B‐producing cells. However, alcohol consumption decreased the expression of perforin in spleen and liver. Taken together, chronic alcohol consumption exacerbates cytomegalovirus infection via impairing nonspecific and specific NK cell activation, specifically IFN‐γ and perforin production.
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