A mosquito salivary gland protein partially inhibits Plasmodium sporozoite cell traversal and transmission

Tyler R Schleicher,Alison Rembisz,Abhai K Tripathi,Samuel Craft,Yue Li,Godfree Mlambo,Photini Sinnis,Peter Cresswell,Jing Yang,Madeleine Hamilton,Erol Fikrig,George Dimopoulos,Morven Graham,Marianna Freudzon

doi:10.1038/s41467-018-05374-3

Tyler R Schleicher, Alison Rembisz + Show 12 more

Open Access

https://doi.org/10.1038/s41467-018-05374-3

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Abstract

The key step during the initiation of malaria is for motile Plasmodium parasites to exit the host dermis and infect the liver. During transmission, the parasites in the form of sporozoites, are injected together with mosquito saliva into the skin. However, the contribution of vector saliva to sporozoite activity during the establishment of the initial infection of the liver is poorly understood. Here we identify a vector protein by mass spectrometry, with similarity to the human gamma interferon inducible thiol reductase (GILT), that is associated with saliva sporozoites of infected Anopheles mosquitoes and has a negative impact on the speed and cell traversal activity of Plasmodium. This protein, referred to as mosquito GILT (mosGILT) represents an example of a protein found in mosquito saliva that may negatively influence sporozoite movement in the host and could lead to new approaches to prevent malaria.

Highlights

The key step during the initiation of malaria is for motile Plasmodium parasites to exit the host dermis and infect the liver
We show a mosquito salivary glands (SGs) protein with homology to the human gamma interferon inducible thiol reductase (GILT) that interacts with the surface of Plasmodium sporozoites as they are expelled from Anopheles mosquito SGs
We found that this mosquito GILT-like protein can partially reduce the speed and cell traversal activity of both human and rodent Plasmodium sporozoites

Summary

Introduction

The key step during the initiation of malaria is for motile Plasmodium parasites to exit the host dermis and infect the liver. We identify a vector protein by mass spectrometry, with similarity to the human gamma interferon inducible thiol reductase (GILT), that is associated with saliva sporozoites of infected Anopheles mosquitoes and has a negative impact on the speed and cell traversal activity of Plasmodium This protein, referred to as mosquito GILT (mosGILT) represents an example of a protein found in mosquito saliva that may negatively influence sporozoite movement in the host and could lead to new approaches to prevent malaria. The partial inhibition of these critical motility components modestly influences the ability of the sporozoites to migrate to the liver and establish a normal hepatic infection This vector-parasite interaction may represent an example of how Plasmodium sporozoites optimize the number of parasites required to complete their life cycle or could suggest a lingering effect of the vector innate immune response that continues to limit parasite activity during transmission. Overall, characterizing the interaction between mosquito GILT and Plasmodium sporozoites could potentially help uncover new pathways associated with motility regulation of Plasmodium parasites and lead to the design of novel therapeutics to prevent malaria transmission

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