Evaluation of the functional importance of Natterin family proteins in the activation of the inflammasome in zebrafish

• Grant number: 21/06084-8
• Support Opportunities: Regular Research Grants
• Duration: December 01, 2021 - November 30, 2023
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Carla Lima da Silva
• Grantee: Carla Lima da Silva
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The Natterin family of proteins was found for the first time in the venom gland of T. nattereri in five orthologous which present in the C-terminal portion an aerolysin domain, thus being able to interact with other proteins to form functional complexes involved in the engulfment of pathogens microbials, intracellular trafficking and phagosome modulation. The aerolysin family belongs to a large class of pore-forming proteins, considered the main virulence factor for severe inflammatory diseases in humans and animals. They have the ability to bind to the membrane of target cells and trigger from cell death to cell survival with the activation of phosphorylation cascades and inflammasome activation. Inflammasomes are complexes formed by multiple proteins and are involved in the perception of infection and activation of the protective inflammatory response. Studies from our group point to the involvement of components of the inflammasome complex in the regulation of neutrophils dependent on IL-1 induced by Natterin. In addition to venomous fish, gene sequences and natterin-like proteins were also identified in non-venomous species such as zebrafish, an excellent model for innate immunity studies and highly viable for genetic manipulation. Thus, to validate the importance of Natterin in the innate immune response regulation network, we propose to use zebrafish as a model organism for infection using embryos silenced with natterin-like proteins by CRISPR/Cas9 or rescued with mimetic mRNAs for evaluation of response to bacterial infection and consequent activation of the inflammasome complex. (AU)