Efferocytosis of lymphocytes induced by Aedes aegypti saliva: using CRISPR/Cas9 system to study the mechanisms involved

Abstract

The saliva of female Aedes aegypti is constituted by a mixture of molecules that participate in the combat against the host hemostatic and immune system during blood feeding, facilitating the ingestion of blood and inhibiting factors that can prevent proper feeding. Pathogens can take advantage of this saliva peculiarity to settle in the host and cause disease. Among the activities present in the vector saliva, there is a rapid, potent, and selective cytotoxic activity on lymphocytes recently described by our group, mediated by a molecule present only in female saliva of this species. It is possible that, in vivo, the accumulation of apoptotic cells in the tissue results in phagocytosis of these cells by specialized phagocytes as macrophages and dendritic cells, a process known as efferocytosis, causing a suppression of cells from the host immune system. In this project, we aim to study the role of efferocytosis as a consequence of the cytotoxic activity found in A. aegypti saliva. In addition, we intend to use the CRISPR/Cas9 system to generate a transgenic mosquito strain lacking the molecule described with cytotoxic potential for lymphocytes and thus, observe its effects on mosquito blood feeding and fecundity. These studies might generate the required knowledge on the microenvironment created by saliva during the bite and thus allow future studies to generate new alternatives to combat the mosquito and the pathogens transmitted by these vectors.