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Infection length and host environment influence on Plasmodium falciparum dry season reservoir.
EMBO Molecular Medicine ( IF 9.0 ) Pub Date : 2024-09-16 , DOI: 10.1038/s44321-024-00127-w
Carolina M Andrade,Manuela Carrasquilla,Usama Dabbas,Jessica Briggs,Hannah van Dijk,Nikolay Sergeev,Awa Sissoko,Moussa Niangaly,Christina Ntalla,Emily LaVerriere,Jeff Skinner,Klara Golob,Jeremy Richter,Hamidou Cisse,Shanping Li,Jason A Hendry,Muhammad Asghar,Didier Doumtabe,Anna Farnert,Thomas Ruppert,Daniel E Neafsey,Kassoum Kayentao,Safiatou Doumbo,Aissata Ongoiba,Peter D Crompton,Boubacar Traore,Bryan Greenhouse,Silvia Portugal

Persistence of malaria parasites in asymptomatic hosts is crucial in areas of seasonally-interrupted transmission, where P. falciparum bridges wet seasons months apart. During the dry season, infected erythrocytes exhibit extended circulation with reduced cytoadherence, increasing the risk of splenic clearance of infected cells and hindering parasitaemia increase. However, what determines parasite persistence for long periods of time remains unknown. Here, we investigated whether seasonality affects plasma composition so that P. falciparum can detect and adjust to changing serological cues; or if alternatively, parasite infection length dictates clinical presentation and persistency. Data from Malian children exposed to alternating ~6-month wet and dry seasons show that plasma composition is unrelated to time of year in non-infected children, and that carrying P. falciparum only minimally affects plasma constitution in asymptomatic hosts. Parasites persisting in the blood of asymptomatic children from the dry into the ensuing wet season rarely if ever appeared to cause malaria in their hosts as seasons changed. In vitro culture in the presence of plasma collected in the dry or the wet seasons did not affect parasite development, replication or host-cell remodelling. The absence of a parasite-encoded sensing mechanism was further supported by the observation of similar features in P. falciparum persisting asymptomatically in the dry season and parasites in age- and sex-matched asymptomatic children in the wet season. Conversely, we show that P. falciparum clones transmitted early in the wet season had lower chance of surviving until the end of the following dry season, contrasting with a higher likelihood of survival of clones transmitted towards the end of the wet season, allowing for the re-initiation of transmission. We propose that the decreased virulence observed in persisting parasites during the dry season is not due to the parasites sensing ability, nor is it linked to a decreased capacity for parasite replication but rather a consequence decreased cytoadhesion associated with infection length.

中文翻译:


侵染长度和宿主环境对恶性疟原虫旱季储藏的影响。



疟疾寄生虫在无症状宿主中的持续存在对于季节性中断传播的地区至关重要,恶性疟原虫在雨季之间相隔数月之间架起桥梁。在旱季,受感染的红细胞表现出循环延长,细胞粘附性降低,增加了受感染细胞脾清除的风险,并阻碍了寄生虫血症的增加。然而,是什么决定了寄生虫的长期持久性仍然未知。在这里,我们研究了季节性是否会影响血浆组成,以便恶性疟原虫能够检测并适应不断变化的血清学线索;或者,如果相反,寄生虫感染持续时间决定了临床表现和持续性。暴露于交替 ~6 个月雨季和旱季的马里儿童的数据表明,未感染儿童的血浆组成与一年中的时间无关,并且携带恶性疟原虫对无症状宿主的血浆构成的影响最小。从干旱到随后的雨季,寄生虫一直存在于无症状儿童的血液中,随着季节的变化,很少(如果有的话)在宿主中引起疟疾。在旱季或雨季收集的血浆存在下的体外培养不会影响寄生虫的发育、复制或宿主细胞重塑。在旱季无症状地持续存在的恶性疟原虫和在雨季年龄和性别匹配的无症状儿童中观察到寄生虫的相似特征,进一步支持了寄生虫编码传感机制的缺失。相反,我们显示 P. 在雨季早期传播的恶性无性系存活到下一个旱季结束的机会较低,相比之下,在雨季结束时传播的克隆存活的可能性较高,从而允许重新开始传播。我们提出,在旱季持续存在的寄生虫中观察到的毒力降低不是由于寄生虫的感知能力,也不是与寄生虫复制能力降低有关,而是与感染长度相关的细胞粘附降低的结果。
更新日期:2024-09-16
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