Effects of Aedes aegypti salivary components on the biology of macrophages and potential therapeutical applications.

Abstract

Macrophages are phagocytic cells derived from monocytes, which derive from hematopoietic stem cells in the bone marrow. They are directly engaged in a series of vital biological processes that include the elimination of pathogens, activation of antigen-specific immune responses, tissue repair and regulation of inflammatory and autoimmune processes. During blood feeding, Aedes aegypti female mosquitoes inoculate saliva into the skin of their vertebrate hosts, modulating their immune functions and facilitating disease transmission. Some components with anticoagulant, antiplatelet and vasodilatory activities have been described in the saliva of A. aegypti and act by neutralizing the effects on hemostasis, allowing the blood meal to occur successfully. However, little is known about the molecules responsible for the immunomodulatory activities present in saliva. During the feeding process, macrophages are possibly among the first cells to come into contact with mosquito saliva. Despite this physiological evidence, very little is known on the immunomodulatory effects of saliva from hematophagous arthropods on macrophages in normal conditions and in the presence of microorganisms. Our preliminary results show that A. aegypti salivary gland extract (SGE) is able to induce cellular recruitment mainly characterized by influx of neutrophils and to a lesser extent of mononuclear cells into the peritoneal cavity. Furthermore, the SGE is able to stimulate the production of IL-1beta in unstimulated macrophage cultures and reduce levels of IL-6 and nitric oxide in macrophages activated by LPS plus IFN-gamma. Therefore, the aim of this project is to evaluate the role of salivary components of A. aegypti in murine macrophages, focusing on genomic/transcriptional profiling, molecular and functional aspects of these cells. This information will be included in the database on the functional immunome from A. aegypti saliva, our group's main research line.