Molecular characterization of the lymphocyte death induced by Aedes aegypti saliva and the impact on its efferocytosis in vitro and in vivo

Abstract

The saliva of female Aedes aegypti is constituted by a mixture of molecules that participate of the combat against the host's hemostasis and immune system during blood feeding. Among the activities found in the saliva of this vector, there is a rapid, potent, and selective cytotoxicity to lymphocytes, recently described by our group and mediated by a molecule only present in saliva of the species' females. This cell death is associated with the exposure of phosphatidylserine in the outer plasmatic membrane; however, this information alone does not allow to precisely classify the type of cell death involved. In addition, it is not known whether phagocytes would be able to recognize these dead cells and eliminate them through efferocytosis; the biological outcome of this process is also unknown. In this project, we intend to perform the biochemical and molecular characterization of the lymphocyte death induced by A. aegypti saliva, to determine whether this activity occurs on non-classic lymphocytes, and to evaluate the role of efferocytosis as a consequence of this cytotoxicity both in vitro and in vivo. To do that, lymphocytes incubated with the salivary components will be co-cultivated with macrophages and dendritic cells in vitro and a model of mice exposure to mosquito bites will be employed for in vivo evaluations. This study will improve the comprehension of the microenvironment created by A. aegypti saliva in the host's skin following the bite and its role in the transmission of arboviruses that cause human diseases, contributing with future studies to generate new alternatives to fight the mosquito and the pathogens transmitted by these vectors. (AU)