Effect of Aedes aegypti salivary components on experimental sepsis: neutrophil modulation

• Grant number: 22/16118-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Parasitology - Entomology and Malacology of Parasites and Vectors
• Principal Investigator: Anderson de Sá Nunes
• Grantee: Júlia de Moura Bernardi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Aedes spp. mosquitoes, especially Aedes aegypti, are endemic in several parts of the world, mainly in tropical and subtropical regions. Its presence and dissemination generate an alert, as it is a vector of several arboviruses such as dengue fever, yellow fever, Zika, and chikungunya. The transmission of these diseases occurs during the blood feeding of female mosquitoes and the success of this process depends on overcoming the hemostatic and immune responses of the vertebrate host which act to prevent blood loss and its protection. Therefore, to be able to feed, these insects rely on the molecules present in their saliva, secreted during the blood meal. Bioactive molecules with immunomodulatory, anti-hemostatic, and anti-inflammatory properties havealready been identified in the saliva and salivary gland extract (SGE) of Ae. aegypti, and their use as immunobiologicals in situations of inflammatory and autoimmune diseases has been growing. Considering the immunomodulatory potential identified in the salivary secretion of Ae. aegypti, this project proposes its use in sepsis, a condition in which there is an inadequate and unbalanced functioning of the immune system. The focus of the project will be on the function of neutrophils, taking into account their high prevalence in acute inflammation and their effector mechanisms that can contribute to the worsening of inflammatory conditions and tissue damage, which co-occur with the immunopathogenesis of sepsis. For this, parameters of neutrophil biology will be evaluated in vitro, as well as the in vivo response after sepsis induction and SGE treatment in mice. In addition, we intend to perform a fractionation of the SGE to identify the fraction responsible for the expected immunomodulatory effects.