Identification of functional links between redox homeostasis and immunity

氧化还原稳态与免疫之间功能联系的识别

• 批准号: 311589-2011
• 负责人: Scorza, Tatiana
• 金额: $ 2.19万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=480924
• 关键词: Identification; functional; links; between; redox

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.

这项研究计划的重点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CD4 T细胞。免疫细胞在其正常代谢过程中产生活性氧（ROS），我们现在意识到ROS在这些细胞内部和之间起着传输信号的作用。在许多情况下，细胞会面临过量或持续的ROS产生，这会改变它们的生理和功能。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），而红细胞富含含铁血红素，这是一种强大的氧化剂。在红细胞过度摄取的条件下，如疟疾，血红素的积累诱导氧化应激，改变巨噬细胞的功能。我们假设巨噬细胞与CD4+ T细胞相互作用以对抗疟疾的方式受到血红素的严格控制，并且疟疾寄生虫利用这些改变来确保其生存。该项目的目的是确定这些相互作用发生的机制。这项研究将有助于了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，这些条件还包括疾病和衰老。