Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection.
Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection.
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DOI：
10.1038/nmicrobiol.2016.276
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发表时间：
2017-02-06
影响因子：
28.3
通讯作者：
Langhorne J
中科院分区：
文献类型：
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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
疟疾是由疟原虫属寄生虫引起的。所有感染人类的疟原虫都能造成长期的慢性感染，形成一个传染病库以维持传播。人们普遍认为，慢性感染的维持涉及抗原变异对适应性免疫的逃避。然而，参与这一过程的基因仅在五种人类感染物种中的两种中被鉴定出来：恶性疟原虫和诺氏疟原虫。此外，对这些物种建立慢性感染的早期事件知之甚少。通过啮齿类动物模型，我们证明了在感染种群中，只有少数寄生虫表达几种毒力相关pir基因簇之一，才能建立慢性感染。这一过程发生在不同种类的寄生虫和不同的宿主身上。慢性的建立独立于适应性免疫，因此不同于慢性恶性疟原虫感染的维持机制。此外，我们表明表达不同类型pir基因的寄生虫比例调节建立慢性感染所需的时间。由于pir基因在大多数（如果不是全部的话）疟原虫物种中是共同的，因此这一过程可能是调节慢性感染建立的一种常见方式。
Malaria is caused by parasites of the genus Plasmodium. All human-infecting Plasmodium species can establish long-lasting chronic infections, creating an infectious reservoir to sustain transmission. It is widely accepted that maintenance of chronic infection involves evasion of adaptive immunity by antigenic variation. However, genes involved in this process have been identified in only two of five human-infecting species: P. falciparum and P. knowlesi. Furthermore, little is understood about the early events in establishment of chronic infection in these species. Using a rodent model we demonstrate that only a minority of parasites from among the infecting population, expressing one of several clusters of virulence-associated pir genes, establishes a chronic infection. This process occurs in different species of parasite and in different hosts. Establishment of chronicity is independent of adaptive immunity and therefore different from the mechanism proposed for maintainance of chronic P. falciparum infections. Furthermore, we show that the proportions of parasites expressing different types of pir genes regulate the time taken to establish a chronic infection. Since pir genes are common to most, if not all, species of Plasmodium, this process may be a common way of regulating the establishment of chronic infections.