<i>Plasmodium falciparum</i> evades immunity of anopheline mosquitoes by interacting with a Pfs47 midgut receptor.

Abstract

The surface protein Pfs47 allows <i>Plasmodium falciparum</i> parasites to survive and be transmitted by making them "undetectable" to the mosquito immune system. <i>P. falciparum</i> parasites express Pfs47 haplotypes compatible with their sympatric vectors, while those with incompatible haplotypes are eliminated by the mosquito. We proposed that Pfs47 serves as a "key" that mediates immune evasion by interacting with a mosquito receptor "the lock," which differs in evolutionarily divergent anopheline mosquitoes. Recombinant Pfs47 (rPfs47) was used to identify the mosquito Pfs47 receptor protein (P47Rec) using far-Western analysis. rPfs47 bound to a single 31-kDa band and the identity of this protein was determined by mass spectrometry. The mosquito P47Rec has two natterin-like domains and binds to Pfs47 with high affinity (17 to 32 nM). P47Rec is a highly conserved protein with submicrovillar localization in midgut cells. It has structural homology to a cytoskeleton-interacting protein and accumulates at the site of ookinete invasion. Silencing P47Rec expression reduced <i>P. falciparum</i> infection, indicating that the interaction of Pfs47 with the receptor is critical for parasite survival. The binding specificity of P47Rec from distant anophelines (<i>Anopheles gambiae</i>, <i>Anopheles dirus</i>, <i>and Anopheles albimanus</i>) with Pfs47-Africa (GB4) and Pfs47-South America (7G8) haplotypes was evaluated, and it is in agreement with the previously documented compatibility between <i>P. falciparum</i> parasites expressing different Pfs47 haplotypes and these three anopheline species. Our findings give further support to the role of Pfs47 in the adaptation of <i>P. falciparum</i> to different vectors.