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鉴定伯氏疟原虫裂殖子相关的血影蛋白(MTRAP)作为一个传播阻断抗原。

Characterisation of the merozoite thrombospondin related anonymous protein (MTRAP) of Plasmodium berghei as a transmission-blocking antigen.

机构信息

Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Parasitologia, São Paulo, SP, Brasil.

出版信息

Mem Inst Oswaldo Cruz. 2024 Mar 22;119:e230217. doi: 10.1590/0074-02760230217. eCollection 2024.

Abstract

BACKGROUND

Malaria is an infectious disease caused by protozoan parasites belonging to the genus Plasmodium. Human-to-human transmission depends on a mosquito vector; thus, the interruption of parasite transmission from humans to mosquitoes is an important approach in the fight against malaria. The parasite stages infectious to mosquitoes are the gametocytes, sexual stages that are ingested by the vector during a blood meal and transform into male and female gametes in the midgut. Immunity against sexual stage antigens expressed by gametocytes, gametes, and the zygote formed after fertilisation can interrupt the parasite sexual cycle in the mosquito. This transmission blocking immunity is mediated by specific antibodies ingested during the mosquito blood feed, inhibiting the parasite development in the midgut. Merozoite thrombospondin related anonymous protein (MTRAP) is a merozoite and gametocyte surface protein essential for gamete egress from erythrocytes and for parasite transmission to mosquitoes.

OBJECTIVES

Here, we evaluated the potential of the P. berghei MTRAP to elicit antibodies with the ability to inhibit gamete fertilisation in vitro.

METHODS

We expressed a soluble recombinant PbMTRAP and used it to immunise BALB/c mice. The transmission blocking activity of the anti-rPbMTRAP antibodies was tested through in vivo challenge experiments followed by in vitro conversion assays.

FINDINGS

Immunisations with the rPbMTRAP induced a strong antibody response and the antibodies recognised the native protein by Western Blot and IFA. Anti-rPbMTRAP present in the blood stream of immunised mice partially inhibited gamete conversion into ookinetes.

CONCLUSION

Our results indicate that antibodies to PbMTRAP may reduce but are not sufficient to completely block transmission.

摘要

背景

疟疾是一种由原生动物寄生虫引起的传染病,属于疟原虫属。人际传播依赖于蚊子媒介;因此,中断寄生虫从人类到蚊子的传播是对抗疟疾的重要方法。对蚊子具有感染力的寄生虫阶段是配子体,即通过蚊子吸血时摄入的有性阶段,并在中肠转化为雄性和雌性配子。针对配子体、配子和受精后形成的合子表达的性阶段抗原的免疫可以中断蚊子中的寄生虫有性周期。这种传播阻断免疫是由蚊子吸血时摄入的特异性抗体介导的,抑制了中肠内寄生虫的发育。裂殖体血影蛋白相关的匿名蛋白(MTRAP)是裂殖体和配子体表面蛋白,对于配子从红细胞中逸出和寄生虫向蚊子传播是必不可少的。

目的

在这里,我们评估了 P. berghei MTRAP 引发具有抑制体外配子受精能力的抗体的潜力。

方法

我们表达了一种可溶性重组 PbMTRAP,并将其用于免疫 BALB/c 小鼠。通过体内挑战实验和体外转化实验测试了抗-rPbMTRAP 抗体的阻断传播活性。

结果

rPbMTRAP 免疫诱导了强烈的抗体反应,并且抗体通过 Western Blot 和 IFA 识别天然蛋白。免疫小鼠血液中的抗-rPbMTRAP 部分抑制了配子转化为动合子。

结论

我们的结果表明,针对 PbMTRAP 的抗体可能会减少但不足以完全阻断传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ede/10959096/46bd31d8cbdb/1678-8060-mioc-119-e230217-gf1.jpg

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