The human malaria parasite Pfs47 gene mediates evasion of the mosquito immune system.

The human malaria parasite Pfs47 gene mediates evasion of the mosquito immune system.
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DOI:
10.1126/science.1235264
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发表时间:
2013-05-24
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Barillas-Mury C
Barillas-Mury C
中科院分区:
其他
文献类型:
--
作者:
Molina-Cruz A;Garver LS;Alabaster A;Bangiolo L;Haile A;Winikor J;Ortega C;van Schaijk BC;Sauerwein RW;Taylor-Salmon E;Barillas-Mury C

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表面蛋白 Pfs47 介导恶性疟原虫逃避冈比亚按蚊补体样免疫系统。冈比亚按蚊传播恶性疟原虫的效率非常高,导致撒哈拉以南非洲地区人类疟疾感染的流行率非常高。结合遗传图谱、连锁群选择和功能基因组学,将 Pfs47 鉴定为恶性疟原虫基因,该基因允许寄生虫在不激活蚊子免疫系统的情况下感染冈比亚疟原虫。 Pfs47 的破坏大大降低了蚊子中寄生虫的存活率,并且这种表型可以通过寄生虫的遗传互补或通过破坏蚊子补体样系统来恢复。 Pfs47 抑制中肠硝化反应,这对于激活类补体系统至关重要。我们提供了直接的实验证据,表明 Pfs47 介导的免疫逃避对于冈比亚疟原虫有效传播人类疟疾至关重要。
The surface protein Pfs47 mediates Plasmodium falciparum evasion of the Anopheles gambiae complement-like immune system. Plasmodium falciparum transmission by Anopheles gambiae mosquitoes is remarkably efficient, resulting in a very high prevalence of human malaria infection in sub-Saharan Africa. A combination of genetic mapping, linkage group selection, and functional genomics was used to identify Pfs47 as a P. falciparum gene that allows the parasite to infect A. gambiae without activating the mosquito immune system. Disruption of Pfs47 greatly reduced parasite survival in the mosquito and this phenotype could be reverted by genetic complementation of the parasite or by disruption of the mosquito complement-like system. Pfs47 suppresses midgut nitration responses that are critical to activate the complement-like system. We provide direct experimental evidence that immune evasion mediated by Pfs47 is critical for efficient human malaria transmission by A. gambiae.
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