The role of CD14 receptor on the metabolic regulation of macrophages stimulated with the venom from Tityus serrulatus scorpion

Abstract

The venom of Tituys serrulatus scorpion (TsV) is constituted by diverse compounds, which interact with innate immune cells and triggers signaling cascades that culminate on the inflammatory process. Envenoming induces alterations in several organs, deregulate ionic channels and can be fatal. Recent studies from our group described that macrophages are one of the main innate immune cells to recognize TsV. This process is performed by molecular pattern recognition receptors, highlighting the CD14 receptor present in these cell surfaces, and when activated, macrophages produce pro-inflammatory mediators. Recent observations implicate CD14 on a general metabolic regulation, since CD14-deficient animals do not become obese and they do not develop insulin resistance or cardiac complications associated to obesity. However, the molecular mechanisms by which CD14 coordinates the metabolic activity of immune system cells have not been elucidated. In this project, we will investigate the role of CD14 on the metabolism of bone marrow derived macrophages and peritoneal macrophages of C57BL/6 and CD14-/- after the stimulation with TsV or LPS. We will evaluate metabolic alterations resulting from the two stimuli, which will be compared between bone marrow derived macrophages or resident on the peritoneal cavity. For this purpose, we will use high resolution mass spectrometry coupled with liquid chromatography, a state-of-art technology on the field of metabolomics and systems biology. This project has great potential to reveal metabolic pathways and molecular mechanisms induced by TsV, how these processes are regulated by CD14 receptor, and for the design of new therapeutic strategies on the envenoming by TsV and related diseases/conditions.