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通过对冈比亚按蚊循环血细胞的全基因组分析发现疟原虫调节剂。

Discovery of Plasmodium modulators by genome-wide analysis of circulating hemocytes in Anopheles gambiae.

机构信息

Faculty of Natural Sciences, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, South Kensington Campus, Imperial College London, London SW7 2AZ, United Kingdom.

出版信息

Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21270-5. doi: 10.1073/pnas.0909463106. Epub 2009 Nov 25.

DOI:10.1073/pnas.0909463106
PMID:19940242
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2783009/
Abstract

Insect hemocytes mediate important cellular immune responses including phagocytosis and encapsulation and also secrete immune factors such as opsonins, melanization factors, and antimicrobial peptides. However, the molecular composition of these important immune cells has not been elucidated in depth, because of their scarcity in the circulating hemolymph, their adhesion to multiple tissues and the lack of primary culture methods to produce sufficient material for a genome-wide analysis. In this study, we report a genome-wide molecular characterization of circulating hemocytes collected from the hemolymph of adult female Anopheles gambiae mosquitoes--the major mosquito vector of human malaria in subSaharan Africa. Their molecular profile identified 1,485 transcripts with enriched expression in these cells, and many of these genes belong to innate immune gene families. This hemocyte-specific transcriptome is compared to those of Drosophila melanogaster and two other mosquitoes, Aedes aegypti and Armigeres subalbatus. We report the identification of two genes as ubiquitous hemocyte markers and several others as hemocyte subpopulation markers. We assess, via an RNAi screen, the roles in development of Plasmodium berghei of 63 genes expressed in hemocytes and provide a molecular comparison of the transcriptome of these cells during malaria infection.

摘要

昆虫血细胞介导体液免疫的重要反应,包括吞噬作用和包被作用,也分泌免疫因子,如调理素、黑化因子和抗菌肽。然而,由于这些重要免疫细胞在循环血液中的数量稀少,它们与多种组织黏附,以及缺乏原代培养方法来产生足够的基因组分析材料,因此它们的分子组成尚未得到深入阐明。在这项研究中,我们报告了从成年雌性冈比亚按蚊(撒哈拉以南非洲地区人类疟疾的主要蚊子传播媒介)血液中的血液中收集的循环血细胞的全基因组分子特征。它们的分子特征确定了 1485 个在这些细胞中富集表达的转录本,其中许多基因属于先天免疫基因家族。这个血细胞特异性转录组与黑腹果蝇(Drosophila melanogaster)和另外两种蚊子(埃及伊蚊和中华按蚊)的转录组进行了比较。我们报告了两种基因作为普遍存在的血细胞标记物的鉴定,以及其他几种作为血细胞亚群标记物的鉴定。我们通过 RNAi 筛选评估了在疟原虫感染过程中 63 个在血细胞中表达的基因对疟原虫伯格氏疟原虫(Plasmodium berghei)发育的作用,并提供了这些细胞在转录水平上对疟疾感染的比较。

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本文引用的文献

1
Genome-wide transcriptomic profiling of Anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and Plasmodium berghei infection.冈比亚按蚊血细胞的全基因组转录组分析揭示了细菌攻击和伯氏疟原虫感染后病原体特异性特征。
BMC Genomics. 2009 Jun 5;10:257. doi: 10.1186/1471-2164-10-257.
2
Anopheles fibrinogen-related proteins provide expanded pattern recognition capacity against bacteria and malaria parasites.按蚊纤维蛋白原相关蛋白对细菌和疟原虫具有增强的模式识别能力。
J Biol Chem. 2009 Apr 10;284(15):9835-44. doi: 10.1074/jbc.M807084200. Epub 2009 Feb 4.
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Immunoglobulin superfamily members play an important role in the mosquito immune system.免疫球蛋白超家族成员在蚊子免疫系统中发挥着重要作用。
Dev Comp Immunol. 2008;32(5):519-31. doi: 10.1016/j.dci.2007.09.007. Epub 2007 Nov 6.
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OrthoDB: the hierarchical catalog of eukaryotic orthologs.OrthoDB:真核生物直系同源基因的分层目录。
Nucleic Acids Res. 2008 Jan;36(Database issue):D271-5. doi: 10.1093/nar/gkm845. Epub 2007 Oct 18.
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Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes.疾病传播媒介蚊子中免疫相关基因和通路的进化动力学
Science. 2007 Jun 22;316(5832):1738-43. doi: 10.1126/science.1139862.
6
Efficiency of salivary gland invasion by malaria sporozoites is controlled by rapid sporozoite destruction in the mosquito haemocoel.疟原虫子孢子侵入唾液腺的效率受蚊子血腔中快速的子孢子破坏控制。
Int J Parasitol. 2007 May;37(6):673-81. doi: 10.1016/j.ijpara.2006.12.007. Epub 2006 Dec 27.
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Characterization of hemocytes from the mosquitoes Anopheles gambiae and Aedes aegypti.冈比亚按蚊和埃及伊蚊血细胞的特征分析。
Insect Biochem Mol Biol. 2006 Dec;36(12):891-903. doi: 10.1016/j.ibmb.2006.08.010. Epub 2006 Sep 16.
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Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei.增强冈比亚按蚊依赖核因子κB的基础免疫力可阻断伯氏疟原虫的发育。
Immunity. 2006 Oct;25(4):677-85. doi: 10.1016/j.immuni.2006.08.019.