Identification of functional links between redox homeostasis and immunity

这项研究计划的中心是研究氧化剂如何影响免疫细胞的功能，特别是巨噬细胞和CD4T细胞。免疫细胞在其正常代谢过程中产生活性氧物种(ROS)，我们现在意识到ROS在这些细胞内部和之间起着传递信号的作用。在许多情况下，细胞面临过量或持续的ROS产生，这改变了他们的生理和功能。巨噬细胞特别容易受到氧化应激的影响，因为它们专门清除受损的红细胞(RBC)，红细胞含有丰富的含铁血红素，这是一种强大的氧化剂。在过度摄取红细胞的情况下，如疟疾，血红素的积累会诱导氧化应激，并改变巨噬细胞的功能。我们假设巨噬细胞与CD4+T细胞相互作用抗击疟疾的方式受到血红素的严格控制，疟疾寄生虫利用这些变化来确保其生存。这个项目的目的是确定这些相互作用发生的机制。这项研究将有助于理解氧化剂如何在与氧化应激相关的条件下调节免疫细胞的功能，氧化应激也包括疾病和衰老。

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.