Hydroxyl functionalized multi-walled carbon nanotubes modulate immune responses without increasing 2009 pandemic influenza A/H1N1 virus titers in infected mice.
Hydroxyl functionalized multi-walled carbon nanotubes modulate immune responses without increasing 2009 pandemic influenza A/H1N1 virus titers in infected mice.
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DOI：
10.1016/j.taap.2020.115167
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发表时间：
2020-10-01
影响因子：
3.8
通讯作者：
Sabo-Attwood T
中科院分区：
文献类型：
--
作者：
Chen H;Humes ST;Rose M;Robinson SE;Loeb JC;Sabaraya IV;Smith LC;Saleh NB;Castleman WL;Lednicky JA;Sabo-Attwood T
越来越多的碳纳米管(CNTs)的使用已经引起了人们对其与不良健康影响的关注。很少有研究探讨碳纳米管如何影响宿主对病原体，特别是呼吸道病毒的易感性。我们报道，肺细胞和小鼠暴露于原始的单壁碳纳米管(SWCNTs)会导致H1N1流感病毒A/墨西哥/4108/2009株(IAV)效价显著增加，同时抑制抗病毒免疫反应。在目前的研究中，我们调查了羟基多壁碳纳米管(MWCNTs)是否会导致类似的结果。C57BL/6小鼠第0天暴露于20μg多壁碳纳米管，第3天暴露于IAV，第7天采集标本，观察肺组织的病理变化、病毒滴度、免疫相关基因表达，并定量检测肺泡灌洗液中细胞分类计数和细胞因子、趋化因子水平。单只多壁碳纳米管引起轻微炎症，免疫标志物没有明显变化，而单独IAV则表现出典型的感染相关炎症、病理和滴度。与单纯IAV相比，联合暴露(MWCNT+IAV)并未改变免疫细胞的滴度或免疫细胞图谱，但增加了IL-1β、肿瘤坏死因子α、GM-CSF、KC、MIPs和RANTES的浓度，并抑制了TLR3、RIG-I、MDA5和IFIT2mRNA的表达。我们的发现表明，多壁碳纳米管可以调节对IAV的免疫反应，但对病毒滴度和轻微的肺损伤没有影响，这一结果与报道的单壁碳纳米管暴露不同。这是首次研究表明，多壁碳纳米管改变控制宿主防御的细胞因子和趋化因子反应，这可能在减轻IAV感染方面发挥更大的作用。
Growing use of carbon nanotubes (CNTs) have garnered concerns regarding their association with adverse health effects. Few studies have probed how CNTs affect a host’s susceptibility to pathogens, particularly respiratory viruses. We reported that exposure of lung cells and mice to pristine single-walled CNTs (SWCNTs) leads to significantly increased influenza virus H1N1 strain A/Mexico/4108/2009 (IAV) titers in concert with repressed antiviral immune responses. In the present study, we investigated if hydroxylated multi-walled CNTs (MWCNTs), would result in similar outcomes. C57BL/6 mice were exposed to 20 μg MWCNTs on day 0 and IAV on day 3 and samples were collected on day 7. We investigated pathological changes, viral titers, immune-related gene expression in lung tissue, and quantified differential cell counts and cytokine and chemokine levels in bronchoalveolar lavage fluid. MWCNTs alone caused mild inflammation with no apparent changes in immune markers whereas IAV alone presented typical infection-associated inflammation, pathology, and titers. The co-exposure (MWCNTs + IAV) did not alter titers or immune cell profiles compared to the IAV only but increased concentrations of IL-1β, TNFα, GM-CSF, KC, MIPs, and RANTES and inhibited mRNA expression of Tlr3, Rig-i, Mda5, and Ifit2. Our findings suggest MWCNTs modulate immune responses to IAV with no effect on the viral titer and modest pulmonary injury, a result different from those reported for SWCNT exposures. This is the first study to show that MWCNTs modify cytokine and chemokine responses that control aspects of host defenses which may play a greater role in mitigating IAV infections.
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影响因子：
5
作者：
Girtsman TA;Beamer CA;Wu N;Buford M;Holian A
通讯作者：
Holian A
影响因子：
5
作者：
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影响因子：
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作者：
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通讯作者：
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小鼠香烟烟雾暴露可调节流感病毒引起的肺部炎症
影响因子：
3.7
作者：
Han Y;Ling MT;Mao H;Zheng J;Liu M;Lam KT;Liu Y;Tu W;Lau YL
通讯作者：
Lau YL
影响因子：
2.1
作者：
Fujita K;Fukuda M;Endoh S;Maru J;Kato H;Nakamura A;Shinohara N;Uchino K;Honda K
通讯作者：
Honda K