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The emergence of pathogenic TNF/iNOS producing dendritic cells (Tip-DCs) in a malaria model of acute respiratory distress syndrome (ARDS) is dependent on CCR4.
在急性呼吸窘迫综合征 (ARDS) 的疟疾模型中,产生致病性 TNF/iNOS 的树突状细胞 (Tip-DCs) 的出现依赖于 ccr4。

摘要

Malaria-associated acute respiratory distress syndrome (MA-ARDS) and acute lung injury (ALI) are complications that cause lung damage and often leads to death. The MA-ARDS/ALI is associated with a Type 1 inflammatory response mediated by T lymphocytes and IFN-γ. Here, we used the Plasmodium berghei NK65 (PbN)-induced MA-ALI/ARDS model that resembles human disease and confirmed that lung CD4+ and CD8+ T cells predominantly expressed Tbet and IFN-γ. Surprisingly, we found that development of MA-ALI/ARDS was dependent on functional CCR4, known to mediate the recruitment of Th2 lymphocytes and regulatory T cells. However, in this Type 1 inflammation-ARDS model, CCR4 was not involved in the recruitment of T lymphocytes, but was required for the emergence of TNF-α/iNOS producing dendritic cells (Tip-DCs) in the lungs. In contrast, recruitment of Tip-DCs and development of MA-ALI/ARDS were not altered in CCR2-/- mice. Importantly, we showed that NOS2-/- mice are resistant to PbN-induced lung damage, indicating that reactive nitrogen species produced by Tip-DCs play an essential role in inducing MA-ARDS/ALI. Lastly, our experiments suggest that production of IFN-γ primarily by CD8+ T cells is required for inducing Tip-DCs differentiation in the lungs and the development of MA-ALI/ARDS model.

译文

疟疾相关的急性呼吸窘迫综合征 (MA-ARDS) 和急性肺损伤 (ALI) 是导致肺损伤并经常导致死亡的并发症。MA-ARDS/ALI 与 T 淋巴细胞和 IFN-γ 介导的 1 型炎症反应有关。在这里,我们使用了伯氏疟原虫 NK65 (PbN) 诱导的 MA-ALI/ARDS 模型,该模型类似于人类疾病,并证实肺 CD4 和 CD8 T 细胞主要表达 Tbet 和 IFN-γ。令人惊讶的是,我们发现 MA-ALI/ARDS 的发展依赖于功能性 CCR4,已知 CCR4 介导了 Th2 淋巴细胞和调节性 T 细胞的募集。然而,在这种 1 型炎症-ARDS 模型中,CCR4 没有参与 T 淋巴细胞的募集, 但是在肺部出现产生树突状细胞 (Tip-DCs) 的 TNF-α/iNOS 是必需的。相反,在 CCR2-/-小鼠中,Tip-DCs 的招募和 MA-ALI/ARDS 的发展没有改变。重要的是,我们表明 NOS2-/-小鼠对 PbN 诱导的肺损伤有抵抗力,这表明 Tip-DCs 产生的活性氮在诱导 MA-ARDS/ALI 中起着重要作用。最后,我们的实验表明,主要由 CD8 T 细胞产生的 IFN-γ 对于在肺部诱导 Tip-DCs 分化和 MA-ALI/ARDS 模型的发展是必需的。

acute respiratory distress syndrome

重症 呼吸窘迫 疾病
概述  :  

急性肺损伤(acute lung injury , ALI)及急性呼吸窘迫综合征(acute respiratory distress syndrome , ARDS)是临床上各学科较为常见的急危重症。大量的基础与临床研究使人们对ALI/ARDS的本质和发病机制有了较为深刻的认识,并逐步确立了临床诊断标准和治疗原则,使ALI/ARDS的诊治水平有了较明显的提高。但临床实践表明,ALI/ARDS的病死率仍然居高不下,原因主要是ALI/ARDS的发病机制尚未完全阐明,缺乏早期诊断的特异

acute 英 [əˈkjuːt] 美 [əˈkjuːt]  

释义   adj. 严重的,[医] 急性的;敏锐的;激烈的;尖声的

例句   He is an acute observer. 他是一个敏锐的观察家。

 

Respiratory 英 [rɪˈspɪrət(ə)ri] 美 [ˈrɛspərəˌtɔri]   

释义   adj. 呼吸的

例句   The blocking of these receptors causes paralysis, respiratory failure and death. 这些受体的阻塞将会引起麻痹、呼吸衰竭和死亡。

 

distress 英 [dɪˈstres] 美 [dɪˈstres]   

释义   n. 危难,不幸;贫困,悲痛 ;vt. 使悲痛;使贫困

例句   But I have enough confidence for it to not distress me.  

但是我拥有足够的自信,因此不会因此而苦恼。


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