吸入氧化铜纳米粒子对屋尘螨诱发哮喘的免疫调节作用
2023/08/28
摘要
背景：已有研究表明吸入氧化铜纳米颗粒（CuO NP）会导致肺部炎症。然而，吸入CuO NP后的免疫调节后果尚未得到充分的研究。
目的：我们测试了CuO NP气溶胶对健康，屋尘螨（HDM）所致的哮喘或过敏原免疫治疗（AIT）的哮喘小鼠（BALB/c，雌性）免疫应答的影响。
方法：AIT由含有HDM过敏原和CpG负载纳米颗粒(CpG NPs)的疫苗组成。AIT治疗涉及免疫小鼠（通过皮下（sc）注射；2剂），从第一次接种当天开始，同时暴露于CuO NP气溶胶（超过2周），然后通过sc注射使小鼠致敏两次，随后用鼻内注射HDM提取物致敏小鼠10次。哮喘模型遵循相同的时间表，只是没有进行免疫接种。
结果：CuO NP暴露的健康小鼠显示T1和T2细胞显着减少，并且T-bet Treg细胞升高，甚至在最后暴露于CuO NP后40天。类似地，CuO NP暴露的HDM哮喘模型表现出降低的T2应答和增加的T-bet Treg细胞。相反，CuO NP吸入暴露于AIT治疗的哮喘小鼠导致T2细胞增加。
所有小鼠在HDM刺激结束后24小时进行尸检。
即使在最后一次暴露于CuO np后40天，暴露于CuO NP的健康小鼠的T1和T2细胞也显著减少，T-bet Treg细胞升高。同样，吸入CuO NP的HDM哮喘模型显示T2反应降低，T-bet Treg细胞增加。相反， 吸入CuO NP的 AIT治疗的哮喘小鼠导致T2细胞增加。
结论：综上所述，，吸入CuO NPs的免疫调节作用取决于暴露前的免疫条件。
Immunomodulatory Effects of Subacute Inhalation Exposure to Copper Oxide Nanoparticles in House Dust Mite-Induced Asthma.
Areecheewakul S, Adamcakova-Dodd A, Zacharias ZR,
Abstrast
Background: It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP inhalation exposure have been less explored.
Objective：We tested the effect of CuO NP aerosols on immune responses in healthy, house dust mite (HDM) asthmatic, or allergen immunotherapy (AIT)-treated asthmatic mice (BALB/c, females).
Methods: The AIT consisted of a vaccine comprising HDM allergens and CpG-loaded nanoparticles (CpG NPs). AIT treatment involved mice being immunized (via subcutaneous (sc) injection; 2 doses) while concomitantly being exposed to CuO NP aerosols (over a 2 week period), starting on the day of the first vaccination. Mice were then sensitized twice by sc injection and subsequently challenged with HDM extract 10 times by intranasal instillation. The asthmatic model followed the same timeline except that no immunizations were administered.
Results: All mice were necropsied 24 h after the end of the HDM challenge. CuO NP-exposed healthy mice showed a significant decrease in T1 and T2 cells, and an elevation in T-bet Treg cells, even 40 days after the last exposure to CuO NPs. Similarly, the CuO NP-exposed HDM asthma model demonstrated decreased T2 responses and increased T-bet Treg cells. Conversely, CuO NP inhalation exposure to AIT-treated asthmatic mice resulted in an increase in T2 cells.
Conclusions: In conclusion, immunomodulatory effects of inhalation exposure to CuO NPs are dependent on immune conditions prior to exposure.
背景：已有研究表明吸入氧化铜纳米颗粒（CuO NP）会导致肺部炎症。然而，吸入CuO NP后的免疫调节后果尚未得到充分的研究。
目的：我们测试了CuO NP气溶胶对健康，屋尘螨（HDM）所致的哮喘或过敏原免疫治疗（AIT）的哮喘小鼠（BALB/c，雌性）免疫应答的影响。
方法：AIT由含有HDM过敏原和CpG负载纳米颗粒(CpG NPs)的疫苗组成。AIT治疗涉及免疫小鼠（通过皮下（sc）注射；2剂），从第一次接种当天开始，同时暴露于CuO NP气溶胶（超过2周），然后通过sc注射使小鼠致敏两次，随后用鼻内注射HDM提取物致敏小鼠10次。哮喘模型遵循相同的时间表，只是没有进行免疫接种。
结果：CuO NP暴露的健康小鼠显示T1和T2细胞显着减少，并且T-bet Treg细胞升高，甚至在最后暴露于CuO NP后40天。类似地，CuO NP暴露的HDM哮喘模型表现出降低的T2应答和增加的T-bet Treg细胞。相反，CuO NP吸入暴露于AIT治疗的哮喘小鼠导致T2细胞增加。
所有小鼠在HDM刺激结束后24小时进行尸检。
即使在最后一次暴露于CuO np后40天，暴露于CuO NP的健康小鼠的T1和T2细胞也显著减少，T-bet Treg细胞升高。同样，吸入CuO NP的HDM哮喘模型显示T2反应降低，T-bet Treg细胞增加。相反， 吸入CuO NP的 AIT治疗的哮喘小鼠导致T2细胞增加。
结论：综上所述，，吸入CuO NPs的免疫调节作用取决于暴露前的免疫条件。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(ACS Nano 2023 Aug 08;17(15); doi: 10.1021/acsnano.3c01668.IF: 14.588)
(ACS Nano 2023 Aug 08;17(15); doi: 10.1021/acsnano.3c01668.IF: 14.588)
Immunomodulatory Effects of Subacute Inhalation Exposure to Copper Oxide Nanoparticles in House Dust Mite-Induced Asthma.
Areecheewakul S, Adamcakova-Dodd A, Zacharias ZR,
Abstrast
Background: It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP inhalation exposure have been less explored.
Objective：We tested the effect of CuO NP aerosols on immune responses in healthy, house dust mite (HDM) asthmatic, or allergen immunotherapy (AIT)-treated asthmatic mice (BALB/c, females).
Methods: The AIT consisted of a vaccine comprising HDM allergens and CpG-loaded nanoparticles (CpG NPs). AIT treatment involved mice being immunized (via subcutaneous (sc) injection; 2 doses) while concomitantly being exposed to CuO NP aerosols (over a 2 week period), starting on the day of the first vaccination. Mice were then sensitized twice by sc injection and subsequently challenged with HDM extract 10 times by intranasal instillation. The asthmatic model followed the same timeline except that no immunizations were administered.
Results: All mice were necropsied 24 h after the end of the HDM challenge. CuO NP-exposed healthy mice showed a significant decrease in T1 and T2 cells, and an elevation in T-bet Treg cells, even 40 days after the last exposure to CuO NPs. Similarly, the CuO NP-exposed HDM asthma model demonstrated decreased T2 responses and increased T-bet Treg cells. Conversely, CuO NP inhalation exposure to AIT-treated asthmatic mice resulted in an increase in T2 cells.
Conclusions: In conclusion, immunomodulatory effects of inhalation exposure to CuO NPs are dependent on immune conditions prior to exposure.
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IL-33诱导的中性粒细胞炎症和NETosis是鼻病毒引发的哮喘加重的基础
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