Abstract
Serial blood passage of Plasmodium universally increases parasite virulence, which can be reversed by mosquito transmission. How mosquitoes reset Plasmodium virulence has been unknown. We have shown that mosquito transmission modifies expression of Plasmodium subtelomeric multigene families, including those that code for variant surface antigens (VSA), and transforms the systemic immune response to blood-stage infection. In this way, the mosquito regulates malaria disease severity. Here, we present a model in which expression of multigene families is reset by epigenetic reprogramming of Plasmodium within the mosquito. This prepares the malaria parasite for entry into a new unknown host and transforms the early parasite–host interactions that shape disease severity. Studying the molecular mechanisms that operate outside the human host to regulate Plasmodium virulence is therefore a priority.
Highlights
Mosquitoes Reset Malaria ParasitesSerial blood passage of Plasmodium universally increases parasite virulence, which can be reversed by mosquito transmission
We have recently shown that mosquito transmission modifies gene expression in blood-stage malaria parasites and in this way resets Plasmodium virulence [12]
By recognising this key function of the mosquito, new research avenues open that can accelerate our understanding of the pathogenesis of human malaria
Summary
Serial blood passage of Plasmodium universally increases parasite virulence, which can be reversed by mosquito transmission. We have shown that mosquito transmission modifies expression of Plasmodium subtelomeric multigene families, including those that code for variant surface antigens (VSA), and transforms the systemic immune response to blood-stage infection. In this way, the mosquito regulates malaria disease severity. We present a model in which expression of multigene families is reset by epigenetic reprogramming of Plasmodium within the mosquito. This prepares the malaria parasite for entry into a new unknown host and transforms the early parasite–host interactions that shape disease severity. Studying the molecular mechanisms that operate outside the human host to regulate Plasmodium virulence is a priority
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
