MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract
MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract
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DOI：
10.1016/j.cyto.2019.154895
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发表时间：
2020-02-01
期刊：
影响因子：
3.8
通讯作者：
Enani, Mushira A.
中科院分区：
文献类型：
--
作者：
Alosaimi, Bandar;Hamed, Maaweya E.;Enani, Mushira A.
中东呼吸综合征冠状病毒是一种人类高致病性病毒，与高发病率和病死率有关。炎症反应对MERS-CoV的发病机制和疾病结局有显著影响。然而，在急性MERS-CoV感染期间，几乎检测不到CD 4 T细胞诱导的免疫应答，具有对效应T细胞的有效抑制和抗原呈递的下调。急性重症MERS-CoV感染期间的局部肺免疫应答，特别是Th 1和Th 2相关免疫应答尚未完全了解。在这项研究中，我们提供了第一个洞察到肺的基因表达谱的Th 1和Th 2相关的细胞因子/趋化因子（Th 1和Th 2反应）在急性MERS冠状病毒感染使用RT 2 Profiler PCR阵列。我们还定量了原发性炎性细胞因子/趋化因子的表达水平。我们的研究结果显示，在MERS-CoV感染患者的下呼吸道中，Th 2下调，Th 1免疫应答不足（部分），炎性细胞因子IL-1 α和IL-1 β以及中性粒细胞趋化因子IL-8（CXCL 8）表达水平高。此外，我们在所有纳入的患者中发现了高病毒载量。我们还观察到炎性细胞因子、Th 1和Th 2下调与病死率之间的相关性。Th 1和Th 2应答下调、炎性细胞因子高表达和高病毒载量可能导致肺部炎症、严重感染、肺炎和ARDS的发展以及较高的病死率。进一步研究Th 1和Th 2调节途径的分子机制对于主动疫苗的开发和新的治疗策略的确定至关重要。
MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4 T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1 alpha and IL-1 beta and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.