蚊虫宠幸一次,免疫系统竟要遭殃数天| PLOS子刊
2018/05/22
近日,来自贝勒医学院(Baylor College of Medicine)的最新一项研究表明,被蚊虫叮咬后受影响的免疫细胞类型的数量比之前描述的要多得多。不仅如此,一些蚊虫叮咬的免疫反应可以在叮咬后7天内被检测出来。

Mice with a humanized immune system were used to study the effects of mosquito bites on human cells. The number of immune cell types affected by mosquito saliva appears to be larger than had been suspected from previous animal studies. Also, the new study indicates that some immune responses to mosquito bites can be detected up until seven days post-bite. [Rico-Hesse et al., 2018]

蚊子在吸血时,会将唾液沉积在宿主的皮肤上,即使没有病原体,也会引起免疫反应,这是因为唾液本身含有蛋白质,导致血液中细胞因子水平升高,同时改变免疫细胞亚群的大小。之前研究人员在小鼠模型的研究中已经观察到这种变化,但最近新的研究进一步地描述了蚊虫叮咬对移植人造血干细胞小鼠免疫细胞的影响。

尽管这些发现具有不确定的生物学意义,但它们可以补充早期研究的结果,即蚊子唾液会增强登革热、西尼罗河病毒和其他虫媒病毒感染的致病性。此外,新研究还发现,蚊虫叮咬引起的免疫效应如此持久可能与过敏反应的研究有关。

这项新研究的细节于5月17日发表在《PLOS Neglected Tropical Diseases》杂志上,题为“Mosquito Saliva Alone Has Profound Effects on the Human Immune System”。该论文描述了由通讯作者Rebecca Rico-Hesse博士领导的贝勒团队如何使用流式细胞术和多重细胞因子珠阵列(multiplex cytokine bead array assays)检测,结合详细的统计分析,以探究四只蚊子在叮咬人源化小鼠足垫后免疫细胞功能的微小但显著的变化的。

DOI:https://doi.org/10.1371/journal.pntd.0006439

“我们检测到了Th1和Th2人类免疫反应,以及对血液中细胞因子水平、皮肤和骨髓中免疫细胞组成的延迟效应(在叮咬7天后)。与以前使用不完整的小鼠模型(incomplete mouse model)和唾液腺提取物或针注射唾液的研究相比,这是第一次在被活蚊子叮咬的完整动物中进行此类检测,包括检测人类免疫反应。人类在被活蚊子叮咬的整个动物中的免疫反应。” 作者写道。

此外,在免疫应答的各个阶段,自然杀伤T细胞、自然杀伤细胞、CD8 + T细胞、单核细胞和巨噬细胞的水平也增加了。总体而言,免疫反应的证据持续到了被叮咬7天后,并且在多种组织类型中可见,包括血液、皮肤和骨髓。

“这些结果对研究噬血昆虫唾液、其对人类免疫系统的影响(有或没有病原体传播)以及确定这些蛋白中的哪一种可作为疫苗接种的靶蛋白以试图阻断多种热带疾病的传播具有重要的影响。此外,在人源化骨髓和皮肤细胞中的持久影响还可以解释通过蚊子传播的一些病毒如何能够在这些组织中仍然存活,或者它们如何能够作为复制池(replication reservoirs)。” 作者总结道。

责编:艾曼

参考资料:

Mosquito Spit Disturbs Human Immune Cells for Days

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  • Mosquito saliva alone has profound effects on the human immune system

    Mosquito saliva is a very complex concoction of >100 proteins, many of which have unknown functions. The effects of mosquito saliva proteins injected into our skin during blood feeding have been studied mainly in mouse models of injection or biting, with many of these systems producing results that may not be relevant to human disease. Here, we describe the numerous effects that mosquito bites have on human immune cells in mice engrafted with human hematopoietic stem cells. We used flow cytometry and multiplex cytokine bead array assays, with detailed statistical analyses, to detect small but significant variations in immune cell functions after 4 mosquitoes fed on humanized mice footpads. After preliminary analyses, at different early times after biting, we focused on assessing innate immune and subsequent cellular responses at 6 hours, 24 hours and 7 days after mosquito bites. We detected both Th1 and Th2 human immune responses, and delayed effects on cytokine levels in the blood, and immune cell compositions in the skin and bone marrow, up to 7 days post-bites. These are the first measurements of this kind, with human immune responses in whole animals, bitten by living mosquitoes, versus previous studies using incomplete mouse models and salivary gland extracts or needle injected saliva. The results have major implications for the study of hematophagous insect saliva, its effects on the human immune system, with or without pathogen transmission, and the possibility of determining which of these proteins to target for vaccination, in attempts to block transmission of numerous tropical diseases.

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