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预先存在的病毒特异性 T 淋巴细胞介导的腺病毒对人血 CD14+细胞的感染增强作用。

Preexisting Virus-Specific T Lymphocytes-Mediated Enhancement of Adenovirus Infections to Human Blood CD14+ Cells.

机构信息

School of Life Sciences, University of Science and Technology of China (USTC), Hefei 230027, China.

State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou 510530, China.

出版信息

Viruses. 2019 Feb 13;11(2):154. doi: 10.3390/v11020154.

Abstract

Antigen-specific T lymphocytes play a critical role in controlling viral infections. However, we report here that preexisting virus-specific T cell responses also contribute to promoting adenovirus (Ad) infection. Previously, we found that CD14+ monocytes from Ad-seropositive individuals exhibited an increased susceptibility to Ad infection, when compared with that of Ad-seronegative individuals. But the underlying mechanisms for this enhancement of viral infection are not completely clarified. In this study, we found that the efficacy of Ad infection into CD14+ monocytes was significantly decreased after CD3+ T lymphocytes depletion from PBMC samples of Ad-seropositive individuals. In contrast, adding virus-specific CD3+ T lymphocytes into PBMC samples of Ad-seronegative individuals resulted in a significant increase of infection efficacy. CD3+ T lymphocytes in PBMC samples from Ad-seropositive individuals were more sensitive to be activated by adenovirus stimulus, characterized by upregulation of multiple cytokines and activation markers and also enhancement of cell proliferation. Further studies demonstrated that GM-CSF and IL-4 can promote Ad infection by up-regulating the expression of scavenger receptor 1 (SR-A) and integrins αVβ5 receptor of CD14+ cells. And taken together, these results suggest a novel role of virus-specific T cells in mediating enhancement of viral infection, and provide insights to understand the pathogenesis and complicated interactions between viruses and host immune cells.

摘要

抗原特异性 T 淋巴细胞在控制病毒感染中起着至关重要的作用。然而,我们在这里报告称,先前存在的病毒特异性 T 细胞反应也有助于促进腺病毒(Ad)感染。此前,我们发现与 Ad 血清阴性个体相比,来自 Ad 血清阳性个体的 CD14+单核细胞对 Ad 感染的易感性增加。但这种增强病毒感染的潜在机制尚未完全阐明。在这项研究中,我们发现从 Ad 血清阳性个体的 PBMC 样本中耗尽 CD3+T 淋巴细胞后,Ad 感染 CD14+单核细胞的效率显著降低。相比之下,将病毒特异性 CD3+T 淋巴细胞添加到 Ad 血清阴性个体的 PBMC 样本中会导致感染效率显著增加。来自 Ad 血清阳性个体的 PBMC 样本中的 CD3+T 淋巴细胞对腺病毒刺激更敏感,表现为多种细胞因子和激活标志物的上调,以及细胞增殖的增强。进一步的研究表明,GM-CSF 和 IL-4 可以通过上调 CD14+细胞的清道夫受体 1(SR-A)和整合素 αVβ5 受体来促进 Ad 感染。综上所述,这些结果表明病毒特异性 T 细胞在介导增强病毒感染方面发挥了新的作用,并为理解病毒和宿主免疫细胞之间的发病机制和复杂相互作用提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6611/6409799/8f9daae7356c/viruses-11-00154-g001.jpg

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