Identification of functional links between redox homeostasis and immunity

点击翻译按钮获取中文摘要

This research proposal centers on investigating how oxidants affect the function of immune cells with special emphasis on macrophages and CD4 T cells. Immune cells generate reactive oxygen species (ROS) during their normal metabolism, and we are now realizing that ROS act as transmission signals inside and between these cells. In many situations, cells become confronted to excessive or sustained production of ROS, which modifies their physiology and function. Macrophages are in particular susceptible to oxidative stress as they are specialized in the removal of damaged red blood cells (RBC), which are rich in iron-containing heme, a powerful oxidant. In conditions of excessive uptake of RBC as in malaria, accumulation of heme induces oxidative stress and alters the function of macrophages. We hypothesize that the manner by which macrophages interact with CD4+ T cells to fight malaria is tightly controlled by heme, and that the malaria parasite has taken advantage of these alterations to assure its survival. The aim of this project is to identify the mechanisms by which these interactions occur. This research will contribute to understand how oxidants modulate the function of immune cells in conditions associated to oxidative stress which also include disease and aging.