Plasmodium knowlesi Cytoadhesion Involves SICA Variant Proteins.
Plasmodium knowlesi Cytoadhesion Involves SICA Variant Proteins.
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DOI：
10.3389/fcimb.2022.888496
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
诺氏疟原虫在整个东南亚社区构成健康威胁，目前在马来西亚造成大多数疟疾病例。这种人畜共患寄生虫已在猕猴（恒河猴）中作为严重疟疾感染、慢性和抗原变异的模型进行了研究。疟原虫抗原变异现象是在恒河猴感染过程中首次发现的。疟原虫编码的变异蛋白首先在该物种中被发现，并被发现在感染的红细胞表面表达，然后被命名为裂殖体感染细胞凝集（SICA）抗原。SICA表达显示为脾依赖性的，因为诺氏疟原虫在脾切除的恒河猴中传代后SICA表达丧失。在这里，我们提供了恒河猴纵向诺氏疟原虫感染的数据，并对迄今为止临床参数和22个器官组织血管系统中感染的红细胞隔离进行了最全面的分析。根据对11只恒河猴22种组织类型的组织病理学分析，我们显示了寄生红细胞的比较分布和感染红细胞与内皮细胞的边缘化程度。有趣的是，在胃肠道组织中存在显著更高的寄生虫负荷，并且寄生虫沿着内皮广泛附在边缘，这可能有助于解释诺氏疟原虫疟疾感染患者经常报告的胃肠道症状。此外，这种边缘化没有观察到脾切除恒河猴感染寄生虫不表达SICA蛋白。这项工作提供了直接支持以下观点的数据：诺氏疟原虫亚群可能通过作为配体的SICA变体抗原进行细胞粘附和隔离。这一过程类似于恶性疟原虫表达的相关变体抗原蛋白，即红细胞膜蛋白-1的细胞粘附功能。
Plasmodium knowlesi poses a health threat throughout Southeast Asian communities and currently causes most cases of malaria in Malaysia. This zoonotic parasite species has been studied in Macaca mulatta (rhesus monkeys) as a model for severe malarial infections, chronicity, and antigenic variation. The phenomenon of Plasmodium antigenic variation was first recognized during rhesus monkey infections. Plasmodium-encoded variant proteins were first discovered in this species and found to be expressed at the surface of infected erythrocytes, and then named the Schizont-Infected Cell Agglutination (SICA) antigens. SICA expression was shown to be spleen dependent, as SICA expression is lost after P. knowlesi is passaged in splenectomized rhesus. Here we present data from longitudinal P. knowlesi infections in rhesus with the most comprehensive analysis to date of clinical parameters and infected red blood cell sequestration in the vasculature of tissues from 22 organs. Based on the histopathological analysis of 22 tissue types from 11 rhesus monkeys, we show a comparative distribution of parasitized erythrocytes and the degree of margination of the infected erythrocytes with the endothelium. Interestingly, there was a significantly higher burden of parasites in the gastrointestinal tissues, and extensive margination of the parasites along the endothelium, which may help explain gastrointestinal symptoms frequently reported by patients with P. knowlesi malarial infections. Moreover, this margination was not observed in splenectomized rhesus that were infected with parasites not expressing the SICA proteins. This work provides data that directly supports the view that a subpopulation of P. knowlesi parasites cytoadheres and sequesters, likely via SICA variant antigens acting as ligands. This process is akin to the cytoadhesive function of the related variant antigen proteins, namely Erythrocyte Membrane Protein-1, expressed by Plasmodium falciparum.
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影响因子：
3.7
作者：
Bachmann A;Esser C;Petter M;Predehl S;von Kalckreuth V;Schmiedel S;Bruchhaus I;Tannich E
通讯作者：
Tannich E
旋钮阳性和旋钮阴性疟原虫恶性疟原虫在感染红细胞表面的菌株特异性疟疾抗原的表达上有所不同。
影响因子：
15.3
作者：
Aley, S B;Sherwood, J A;Howard, R J
通讯作者：
Howard, R J
DOI：
10.1084/jem.165.5.1269
发表时间：
1987-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Handunnetti SM;Mendis KN;David PH
通讯作者：
David PH
DOI：
10.1016/s1473-3099(18)30068-9
发表时间：
2018-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Amato R;Pearson RD;Almagro-Garcia J;Amaratunga C;Lim P;Suon S;Sreng S;Drury E;Stalker J;Miotto O;Fairhurst RM;Kwiatkowski DP
通讯作者：
Kwiatkowski DP
影响因子：
64.5
作者：
BARUCH, DI;PASLOSKE, BL;HOWARD, RJ
通讯作者：
HOWARD, RJ