Glycosylation of Trypanosoma cruzi TcI antigen reveals recognition by chagasic sera.

Glycosylation of Trypanosoma cruzi TcI antigen reveals recognition by chagasic sera.
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DOI:
10.1038/s41598-020-73390-9
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发表时间:
2020-10-02
期刊:
影响因子:
4.6
通讯作者:
Miles MA
Miles MA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Murphy N;Rooney B;Bhattacharyya T;Triana-Chavez O;Krueger A;Haslam SM;O'Rourke V;Pańczuk M;Tsang J;Bickford-Smith J;Gilman RH;Tetteh K;Drakeley C;Smales CM;Miles MA

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恰加斯病被认为是拉丁美洲最重要的寄生虫病。原虫制剂克鲁兹锥虫由六个遗传谱系TCI-TcVI组成。克氏毛滴虫在宿主组织中的隔离和复制阻碍了将血统(S)与心肌病和胃肠道病理严重程度联系起来的基因分型。我们基于重组塔氏利什曼原虫小表面抗原(gTSSA-I)在真核细胞中的表达,描述了亚马逊北部主要血统TCI的特异性血清学,以允许真实的糖基化和抗原的结构。TCI疫区血清可识别gTSSA-I(74/146;50.7%),与gTSSA-II/V/VI重组抗原的常见成分无交叉反应。GTSSA-I糖基化的化学(高碘酸盐)氧化消除了抗原性,但在构象热变性后保留了抗原性。相反,非疟疾流行血清对gTSSA-I的非特异性识别通过热变性而取消。TCI特异性血清学有助于研究谱系和不同临床表现之间的关系。在寻找免疫原性抗原的过程中,糖基化不能被忽略。
Chagas disease is considered the most important parasitic disease in Latin America. The protozoan agent, Trypanosoma cruzi, comprises six genetic lineages, TcI-TcVI. Genotyping to link lineage(s) to severity of cardiomyopathy and gastrointestinal pathology is impeded by the sequestration and replication of T. cruzi in host tissues. We describe serology specific for TcI, the predominant lineage north of the Amazon, based on expression of recombinant trypomastigote small surface antigen (gTSSA-I) in the eukaryote Leishmania tarentolae, to allow realistic glycosylation and structure of the antigen. Sera from TcI-endemic regions recognised gTSSA-I (74/146; 50.7%), with no cross reaction with common components of gTSSA-II/V/VI recombinant antigen. Antigenicity was abolished by chemical (periodate) oxidation of gTSSA-I glycosylation but retained after heat-denaturation of conformation. Conversely, non-specific recognition of gTSSA-I by non-endemic malaria sera was abolished by heat-denaturation. TcI-specific serology facilitates investigation between lineage and diverse clinical presentations. Glycosylation cannot be ignored in the search for immunogenic antigens.
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