Immunomodulation of experimental autoimmune encephalomyelitis by salivary gland extract of Aedes aegypti

Abstract

During a successful blood feeding of A. aegypti female mosquito, various biologically active components of saliva interact with the host and alter a number of hematological and immunological factors. Together, these modifications can lead to profound changes in the course of some infectious and autoimmune diseases. In this sense, several immunomodulatory activities have been described in the saliva of bloodsucking insects in recent years. Thus, the aim of this proposal is to analyze the modulation of experimental autoimmune encephalomyelitis (EAE), a model for studying of multiple sclerosis, by the salivary components of the mosquito A. aegypti in C57BL/6 mice. A. aegypti salivary gland extract (SGE) will be produced from the salivary glands of females with 5-7 days after emerging. This material will be sonicated, centrifuged, sterilized, the protein content will be measured and stored at -80 °C until use. To study the in vivo activity of SGE on EAE (induced by immunization with MOG p35-55), we will use two distinct approaches. In the preventive approach, a group of immunized animals will receive a daily treatment with SGE starting at the day two of immunization, administered intravenously. In therapeutic approach, animals immunized will be treated with SGE in the same dose and route at the beginning of the first signs of the disease, determined by a well known clinical score. The disease progression will be monitored for 30 days and compared with a group of animals given only vehicle (PBS) in the same treatment regimen and route. In both cases, some animals will be euthanized for histopathological analysis of the central nervous system (CNS) as well as parameters related to host immunity, such as cytokine production by cells from lymph nodes and frequencies of lymphocyte subpopulations in these organs. We also will perform a fractionation of the SGE in order to identify one or more fractions in an attempt to characterize biologically active molecules in this model. We hope to demonstrate the activity of A. aegypti SGE in a model of autoimmunity, while we characterize new potential immunomodulatory molecules in mosquito saliva. (AU)