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恶性疟原虫 var 基因表达的同质性作为疟疾自然获得性免疫水平不同下宿主-寄生虫关系的标志物。

Plasmodium falciparum var gene expression homogeneity as a marker of the host-parasite relationship under different levels of naturally acquired immunity to malaria.

机构信息

Pathogen, Vector and Human Biology Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.

出版信息

PLoS One. 2013 Jul 29;8(7):e70467. doi: 10.1371/journal.pone.0070467. Print 2013.

DOI:10.1371/journal.pone.0070467
PMID:23922996
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3726600/
Abstract

Acquired immunity to Plasmodium falciparum infection causes a change from frequent, sometimes life-threatening, malaria in young children to asymptomatic, chronic infections in older children and adults. Little is known about how this transition occurs but antibodies to the extremely diverse PfEMP1 parasite antigens are thought to play a role. PfEMP1 is encoded by a family of 60 var genes that undergo clonal antigenic variation, potentially creating an antigenically heterogeneous infecting population of parasites within the host. Previous theoretical work suggests that antibodies to PfEMP1 may play a role in "orchestrating" their expression within infections leading to sequential, homogeneous expression of var genes, and prolonged infection chronicity. Here, using a cloning and sequencing approach we compare the var expression homogeneity (VEH) between isolates from children with asymptomatic and clinical infections. We show that asymptomatic infections have higher VEH than clinical infections and a broader host antibody response. We discuss this in relation to the potential role of host antibodies in promoting chronicity of infection and parasite survival through the low transmission season.

摘要

获得性免疫对疟原虫感染的抵抗力导致儿童期频繁、有时危及生命的疟疾转变为年长儿童和成人无症状、慢性感染。目前尚不清楚这种转变是如何发生的,但人们认为针对极度多样化 PfEMP1 寄生虫抗原的抗体发挥了作用。PfEMP1 由一个包含 60 个 var 基因的家族编码,这些基因经历克隆抗原变异,可能在宿主内产生具有不同抗原性的寄生虫感染群体。先前的理论工作表明,针对 PfEMP1 的抗体可能在“协调”它们在感染中的表达方面发挥作用,导致 var 基因的顺序、同质表达,并延长感染的慢性。在这里,我们使用克隆和测序方法比较了无症状和临床感染儿童分离株之间的 var 表达同质性(VEH)。我们表明,无症状感染的 VEH 高于临床感染,宿主抗体反应也更广。我们讨论了这与宿主抗体在通过低传播季节促进感染慢性化和寄生虫存活方面的潜在作用的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/c91752cf4299/pone.0070467.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/c5eeb1520074/pone.0070467.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/cc27d0a867cf/pone.0070467.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/03bee79e85ac/pone.0070467.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/6cdfde0adf47/pone.0070467.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/c91752cf4299/pone.0070467.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/c5eeb1520074/pone.0070467.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/cc27d0a867cf/pone.0070467.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/03bee79e85ac/pone.0070467.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/6cdfde0adf47/pone.0070467.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1e/3726600/c91752cf4299/pone.0070467.g005.jpg

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