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The Human Malaria Parasite Pfs47 Gene Mediates Evasion of the Mosquito Immune System

Science  24 May 2013:
Vol. 340, Issue 6135, pp. 984-987
DOI: 10.1126/science.1235264

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Malaria Cloak and Dagger

Mosquitoes have a complex immune system capable of effective antiparasite responses; however, malaria transmission is still highly efficient. Molina-Cruz et al. (p. 984, published online 9 May; see the Perspective by Philip and Waters) show that Plasmodium falciparum has a gene product, Pfs47, that makes the parasite's ookinetes “invisible” to the mosquito immune system. Disruption of this mechanism could potentially be used to block malaria transmission.

Abstract

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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