Variant surface antigens of Plasmodium chabaudi as a model to study antigenic variation in P. vivax

查鲍迪疟原虫表面抗原变异体作为研究间日疟原虫抗原变异的模型

• 批准号: MC_EX_G0901345
• 负责人: Jean Langhorne
• 金额: $ 20.54万
• 依托单位: The Francis Crick Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_EX_G0901345
• 关键词: Variant; surface; antigens; Plasmodium; chabaudi

Plasmodium vivax Malaria can cause severe illness in people. The parasite is thought to stick to tissues and organs resulting in disease. P. vivax is a chronic infection resulting in low levels of parasites in blood for a long time. One reason for this is that the parasite avoids the host?s antibody response. The malaria parasite lives for much of its life in red blood cells (RBC), and should be invisible to host antibodies. However, the parasite needs to communicate with the environment outside the RBC, and therefore produces molecules present on the RBC surface for this. This means that the parasite is no longer invisible and can be eliminated by antibodies. To avoid this, the proteins at the RBC surface constantly change by switching on and off genes that code for different variants, so that the parasite stays one step ahead of the antibody response. We will use a mouse model of malaria to investigate how the expression of these proteins is regulated, whether they are recognized by antibodies, and whether they are responsible for adhesion in organs. It might possible to use this knowledge to prevent adhesion and thus disease, and to develop vaccines.

间日疟原虫疟疾可导致严重的疾病。这种寄生虫被认为粘附在组织和器官上，导致疾病。间日疟原虫是一种慢性感染，导致血液中的寄生虫水平长期处于低水平。其中一个原因是寄生虫避开了宿主？s抗体应答。疟疾寄生虫的大部分时间都生活在红细胞（RBC）中，宿主抗体应该看不见。然而，寄生虫需要与红细胞外的环境沟通，因此在红细胞表面产生分子。这意味着寄生虫不再是不可见的，可以通过抗体消除。为了避免这种情况，红细胞表面的蛋白质通过打开和关闭编码不同变体的基因而不断变化，因此寄生虫比抗体反应领先一步。我们将使用疟疾小鼠模型来研究这些蛋白质的表达是如何调节的，它们是否被抗体识别，以及它们是否负责器官中的粘附。也许可以利用这些知识来预防粘连，从而预防疾病，并开发疫苗。

项目成果

Characterization of the Plasmodium Interspersed Repeats (PIR) proteins of Plasmodium chabaudi indicates functional diversity.

• DOI: 10.1038/srep23449
• 发表时间: 2016-03-21
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Yam XY;Brugat T;Siau A;Lawton J;Wong DS;Farah A;Twang JS;Gao X;Langhorne J;Preiser PR
• 通讯作者: Preiser PR

Characterization and gene expression analysis of the cir multi-gene family of Plasmodium chabaudi chabaudi (AS).

• DOI: 10.1186/1471-2164-13-125
• 发表时间: 2012-03-29
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Lawton J;Brugat T;Yan YX;Reid AJ;Böhme U;Otto TD;Pain A;Jackson A;Berriman M;Cunningham D;Preiser P;Langhorne J
• 通讯作者: Langhorne J

A comprehensive evaluation of rodent malaria parasite genomes and gene expression.

• DOI: 10.1186/s12915-014-0086-0
• 发表时间: 2014-10-30
• 期刊: BMC biology
• 影响因子: 5.4
• 作者: Otto TD;Böhme U;Jackson AP;Hunt M;Franke-Fayard B;Hoeijmakers WA;Religa AA;Robertson L;Sanders M;Ogun SA;Cunningham D;Erhart A;Billker O;Khan SM;Stunnenberg HG;Langhorne J;Holder AA;Waters AP;Newbold CI;Pain A;Berriman M;Janse CJ
• 通讯作者: Janse CJ

Sequestration and histopathology in Plasmodium chabaudi malaria are influenced by the immune response in an organ-specific manner.

• DOI: 10.1111/cmi.12212
• 发表时间: 2014-05
• 期刊: Cellular microbiology
• 影响因子: 3.4
• 作者: Brugat T;Cunningham D;Sodenkamp J;Coomes S;Wilson M;Spence PJ;Jarra W;Thompson J;Scudamore C;Langhorne J
• 通讯作者: Langhorne J

Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection.

• DOI: 10.1038/nmicrobiol.2016.276
• 发表时间: 2017-02-06
• 期刊: Nature microbiology
• 影响因子: 28.3
• 作者: Brugat T;Reid AJ;Lin J;Cunningham D;Tumwine I;Kushinga G;McLaughlin S;Spence P;Böhme U;Sanders M;Conteh S;Bushell E;Metcalf T;Billker O;Duffy PE;Newbold C;Berriman M;Langhorne J
• 通讯作者: Langhorne J