Characterisation of infection associated microRNA and protein cargo in extracellular vesicles of Theileria annulata infected leukocytes.

Characterisation of infection associated microRNA and protein cargo in extracellular vesicles of Theileria annulata infected leukocytes.
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感染的特征在于感染的白细胞的细胞外囊泡中相关的microRNA和蛋白质货物的表征。

DOI:
10.1111/cmi.12969
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发表时间:
2019-01
影响因子:
3.4
通讯作者:
Devaney E
Devaney E
中科院分区:
生物学2区
文献类型:
--
作者:
Gillan V;Simpson DM;Kinnaird J;Maitland K;Shiels B;Devaney E

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原生动物寄生虫Theileria annulata和Theileria parva在细胞内真核病原体中是独一无二的,因为它们在牛宿主细胞中诱导了一种转化样的表型。环状毛滴虫引起热带泰勒氏症,通常是致命的,感染的白细胞会发生转移,并在多个器官形成病灶,导致淋巴系统遭到破坏。胞外小体是细胞外小泡(EV)的一个子集,在许多癌症的转移过程中起着关键作用。在这里,我们通过比较质谱学和microRNA(MiRNA)图谱(分别通过ProteomeXchange,标识符PXD010713和NCBI GEO,登录号GSE118456)表征了来自对照牛淋巴肉瘤细胞系(BL20)和感染毛滴虫(TBL20)的BL20的EV货物。独创性途径分析表明,与BL20对照相比,许多对迁移和细胞外基质消化至关重要的感染相关蛋白在TBL20细胞的EV中上调。还观察到了宿主miRNA的改变,其中许多在肿瘤和/或感染生物学中具有已知的作用。针对肿瘤抑制因子miRNA、BTA-miR-181a和BTA-miR-181b,我们确定了可能的信使RNA靶标,并证实了BTA-miR181a与ICAM-1的相互作用。我们认为EV及其miRNA载体在调控宿主细胞表型和泰勒氏菌感染的病理生物学中起重要作用。
The protozoan parasites Theileria annulata and Theileria parva are unique amongst intracellular eukaryotic pathogens as they induce a transformation‐like phenotype in their bovine host cell. T. annulata causes tropical theileriosis, which is frequently fatal, with infected leukocytes becoming metastatic and forming foci in multiple organs resulting in destruction of the lymphoid system. Exosomes, a subset of extracellular vesicles (EV), are critical in metastatic progression in many cancers. Here, we characterised the cargo of EV from a control bovine lymphosarcoma cell line (BL20) and BL20 infected with T. annulata (TBL20) by comparative mass spectrometry and microRNA (miRNA) profiling (data available via ProteomeXchange, identifier PXD010713 and NCBI GEO, accession number GSE118456, respectively). Ingenuity pathway analysis that many infection‐associated proteins essential to migration and extracellular matrix digestion were upregulated in EV from TBL20 cells compared with BL20 controls. An altered repertoire of host miRNA, many with known roles in tumour and/or infection biology, was also observed. Focusing on the tumour suppressor miRNA, bta‐miR‐181a and bta‐miR‐181b, we identified putative messenger RNA targets and confirmed the interaction of bta‐miR181a with ICAM‐1. We propose that EV and their miRNA cargo play an important role in the manipulation of the host cell phenotype and the pathobiology of Theileria infection.
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