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通过拟蚊大头金蝇唾液诱导免疫细胞 Fas 介导的半胱天冬酶-8 非依赖性细胞凋亡。

Induction of Fas mediated caspase-8 independent apoptosis in immune cells by Armigeres subalbatus saliva.

机构信息

Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, Shantou, People's Republic of China.

出版信息

PLoS One. 2012;7(7):e41145. doi: 10.1371/journal.pone.0041145. Epub 2012 Jul 17.

DOI:10.1371/journal.pone.0041145
PMID:22815944
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3398892/
Abstract

BACKGROUND

It is widely recognized that the introduction of saliva of bloodsucking arthropods at the site of pathogen transmission might play a central role in vector-borne infections. However, how the interaction between salivary components and the host immune system takes place and which physiological processes this leads to has yet to be investigated. Armigeres subalbatus is one of the prominent types of mosquitoes involved in the transmission of parasitic and viral diseases in humans and animals.

METHODOLOGY/PRINCIPAL FINDINGS: Using murine peritoneal macrophages and lymphocytes, and human peripheral mononuclear cells (PBMCs), this study shows that saliva of the female Ar. subalbatus induces apoptosis via interaction with the Fas receptor within a few hours but without activating caspase-8. The process further activates downstream p38 MAPK signaling, a cascade that leads to the induction of apoptosis in capase-3 dependent manner. We further illustrate that Ar. subalbatus saliva suppresses proinflammatory cytokines without changing IL-10 levels, which might happen as a result of apoptosis.

CONCLUSIONS

Our study shows for the first time that saliva-induced apoptosis is the leading phenomenon exerted by Ar.subalbatus that impede immune cells leading to the suppression of their effecter mechanism.

摘要

背景

人们普遍认识到,在病原体传播部位引入吸血节肢动物的唾液可能在虫媒传染病中起核心作用。然而,唾液成分与宿主免疫系统之间的相互作用以及这导致了哪些生理过程尚未得到研究。淡色库蚊是参与人类和动物寄生虫病和病毒性疾病传播的重要蚊种之一。

方法/主要发现:本研究使用鼠腹腔巨噬细胞和淋巴细胞以及人外周血单核细胞(PBMC),表明雌性淡色库蚊的唾液通过与 Fas 受体相互作用在数小时内诱导细胞凋亡,但不会激活 caspase-8。该过程进一步激活下游的 p38 MAPK 信号通路,这一级联反应导致 caspase-3 依赖性的细胞凋亡。我们进一步表明,淡色库蚊的唾液抑制促炎细胞因子而不改变 IL-10 水平,这可能是由于细胞凋亡所致。

结论

我们的研究首次表明,唾液诱导的细胞凋亡是淡色库蚊发挥作用的主要现象,它阻止免疫细胞,从而抑制其效应机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/281bb87bcd4b/pone.0041145.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/20a141dcf34d/pone.0041145.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/0640860c10a8/pone.0041145.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/115412d12590/pone.0041145.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/f69e46dbde1e/pone.0041145.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/f54865f76ba8/pone.0041145.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/3c5b77c173a7/pone.0041145.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/281bb87bcd4b/pone.0041145.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/20a141dcf34d/pone.0041145.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/0640860c10a8/pone.0041145.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/115412d12590/pone.0041145.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/f69e46dbde1e/pone.0041145.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/f54865f76ba8/pone.0041145.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/3c5b77c173a7/pone.0041145.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6020/3398892/281bb87bcd4b/pone.0041145.g007.jpg

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