Aedes albopictus D7 Salivary Protein Prevents Host Hemostasis and Inflammation.

Ines Martin-Martin,Leticia Barion Smith,Eric Calvo,Andrezza Campos Chagas,Anderson Sá-Nunes,Paola Carolina Valenzuela-Leon,Gaurav Shrivastava

doi:10.3390/biom10101372

Abstract

Mosquitoes inject saliva into the host skin to facilitate blood meal acquisition through active compounds that prevent hemostasis. D7 proteins are among the most abundant components of the mosquito saliva and act as scavengers of biogenic amines and eicosanoids. Several members of the D7 family have been characterized at the biochemical level; however, none have been studied thus far in Aedes albopictus, a permissive vector for several arboviruses that causes extensive human morbidity and mortality. Here, we report the binding capabilities of a D7 long form protein from Ae. albopictus (AlboD7L1) by isothermal titration calorimetry and compared its model structure with previously solved D7 structures. The physiological function of AlboD7L1 was demonstrated by ex vivo platelet aggregation and in vivo leukocyte recruitment experiments. AlboD7L1 binds host hemostasis agonists, including biogenic amines, leukotrienes, and the thromboxane A2 analog U-46619. AlboD7L1 protein model predicts binding of biolipids through its N-terminal domain, while the C-terminal domain binds biogenic amines. We demonstrated the biological function of AlboD7L1 as an inhibitor of both platelet aggregation and cell recruitment of neutrophils and eosinophils. Altogether, this study reinforces the physiological relevance of the D7 salivary proteins as anti-hemostatic and anti-inflammatory molecules that help blood feeding in mosquitoes.

Highlights

The Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae), has undergone a dramatic global expansion starting from Southeast Asia to the Americas, Europe, Africa, and the Middle East [1,2]
We demonstrate the functional consequence of scavenging these hemostasis and inflammatory agonists: Biogenic amine binding results in platelet aggregation inhibition whereas leukotriene binding prevents leukocyte recruitment in vivo
AlboD7L1 pretreatment significantly reduced cell infiltration into the peritoneal cavity of mice when compared to control animals. These results suggest that the effect of AlboD7L1 on the recruitment of neutrophils and eosinophils induced by the β-glucan from S. cerevisiae, is due to its inhibitory effect on leukotrienes, especially leukotriene B4 (LTB4) which is a potent stimulant of leukocyte functions including the chemotaxis, chemokinesis, and aggregation of polymorphonuclear leukocytes

Summary

Introduction

The Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae), has undergone a dramatic global expansion starting from Southeast Asia to the Americas, Europe, Africa, and the Middle East [1,2]. Female Ae. albopictus mosquitoes require vertebrate blood for egg development. This mosquito species is an opportunistic feeder which takes blood meals primarily from mammals, but preferentially feeds on humans [8,9]. Aedes albopictus mosquitoes have been reported to feed on domestic and wildlife animals and might serve as bridge vectors by supporting the potential transfer of an acquired pathogen from an infected wild animal to a human host during a subsequent blood-meal [5]

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Results

Conclusion