Sympathetic immunomodulation of the microbicidal action of macrophages and neutrophils

• Grant number: 23/07357-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2023
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Alexandre Alarcon Steiner
• Grantee: Kathia Terumi Kato
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/03418-0 - Hypothermia in Sepsis: causes and consequences, AP.TEM

Abstract

Inflammation is a protective response of the body, coordinated by cells of the immune system, which is extremely important in containing an infectious process and, therefore, must be precisely regulate, as it can cause collateral damage. For this regulation, the adjustments of the inflammatory process occur through the bidirectional interaction between the Central Nervous System (CNS) and the Immune System (IS). In this scenario, the literature highlights the discovery of a pathway called "inflammatory reflex", which would be responsible for modulating acute inflammatory responses through neural pathways, with the splanchnic nerve pathway still little known. Therefore, in this project, we intend to study the role of the splanchnic nerve, a nerve capable of modulating inflammatory responses through sympathetic signaling, on the microbicidal actions of macrophages and neutrophils. In order to study the regulatory role of the splanchnic nerve on the microbicidal actions of macrophages and neutrophils, rats will be submitted to bilateral splanchnicectomy or sham procedure, and then challenged with Escherichia coli or lipopolysaccharide (LPS). The microbicidal actions will be evaluated in vivo, through the mechanisms of phagocytosis and production of reactive oxygen species (ROS) from macrophages and neutrophils by flow cytometry. This cells will be obtained from abdominal organs such as the spleen, liver, intestine and kidney, which are innervated by the splanchnic nerve and also the lung, which has no direct proximity to this nerve. For phagocytosis, the presence of E. coli expressing Green Fluorescent Protein (GFP) within the cells of interest will be detected. Analogously, the production of ROS will be detected through a probe administered prior to the injection of LPS. Furthermore, the effects of two adrenergic antagonists, propranolol and phentolamine, on the microbicidal actions of macrophages and neutrophils will be observed.