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人类基孔肯雅病毒感染的急性期与强烈的固有免疫和 T CD8 细胞激活有关。

The acute phase of Chikungunya virus infection in humans is associated with strong innate immunity and T CD8 cell activation.

机构信息

Centre International de Recherches Médicales de Franceville, BP769, Gabon.

出版信息

J Infect Dis. 2011 Jul 1;204(1):115-23. doi: 10.1093/infdis/jiq006. Epub 2010 Dec 14.

Abstract

BACKGROUND

Rapidly spreading to new regions, including the islands of the Indian Ocean, Central Africa, and Europe, Chikungunya fever is becoming a major problem of public health. Unlike other members of the alphavirus genus, immune responses to Chikungunya virus (CHIKV) have been poorly investigated.

METHODS

We conducted a large ex vivo multiplex study of 50 cytokine, chemokine, and growth factor plasma profiles in 69 acutely infected patients from the Gabonese outbreak of 2007. We also assessed a phenotypic study of T lymphocyte responses during human acute CHIKV infection.

RESULTS

CHIKV infection in humans elicited strong innate immunity involving the production of numerous proinflammatory mediators. Interestingly, high levels of Interferon (IFN) α were consistently found. Production of interleukin (IL) 4, IL-10, and IFN-γ suggested the engagement of the adaptive immunity. This was confirmed by flow cytometry of circulating T lymphocytes that showed a CD8+ T lymphocyte response in the early stages of the disease, and a CD4+ T lymphocyte mediated response in the later stages. For the first time to our knowledge, we found evidence of CD95-mediated apoptosis of CD4+ T lymphocytes during the first 2 days after symptoms onset, ex vivo.

CONCLUSIONS

Together, our findings suggest that strong innate immunity is required to control CHIKV infection.

摘要

背景

基孔肯雅热迅速传播到新的地区,包括印度洋岛屿、中非和欧洲,正在成为一个主要的公共卫生问题。与甲病毒属的其他成员不同,人们对基孔肯雅病毒(CHIKV)的免疫反应研究甚少。

方法

我们对 2007 年加蓬暴发期间的 69 例急性感染患者进行了一项大型的体外多重分析,研究了 50 种细胞因子、趋化因子和生长因子的血浆谱。我们还评估了人类急性 CHIKV 感染期间 T 淋巴细胞反应的表型研究。

结果

人类感染 CHIKV 会引发强烈的先天免疫反应,涉及多种促炎介质的产生。有趣的是,干扰素(IFN)α的水平一直很高。白细胞介素(IL)4、IL-10 和 IFN-γ的产生表明适应性免疫的参与。这通过循环 T 淋巴细胞的流式细胞术得到了证实,该技术显示在疾病的早期阶段存在 CD8+T 淋巴细胞反应,而在后期阶段存在 CD4+T 淋巴细胞介导的反应。据我们所知,这是首次在体外发现 CD4+T 淋巴细胞在症状出现后的头两天发生 CD95 介导的细胞凋亡。

结论

总之,我们的研究结果表明,强烈的先天免疫是控制 CHIKV 感染所必需的。

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