Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
mBio. 2024 Oct 16;15(10):e0305723. doi: 10.1128/mbio.03057-23. Epub 2024 Aug 29.
Macrophages are critical components of the antifungal immune response. Disturbance in the number or function of these innate immune cells can significantly increase susceptibility to invasive fungal infections. Pathogenic fungi cause billions of infections every year and have an unmet clinical need, with many infections associated with unacceptably high mortality rates that primarily affect vulnerable patients with underlying immune defects. Lipid metabolism has been increasingly appreciated to significantly influence macrophage function, particularly of macrophages residing in lipid-rich organs, such as the brain, or macrophages specialized at clearing dead cells including alveolar macrophages in the lungs. In this review, we provide an overview of macrophage lipid metabolism, and discuss how lipid recycling and dysregulation affect key macrophage functions relevant for antifungal immunity including phagocytosis, functional polarization, and inflammasome activation. We focus on the fungal pathogen , as this is the most common cause of death from fungal infection in humans and because several lines of evidence have already linked lipid metabolism in the regulation of and macrophage interactions.
巨噬细胞是抗真菌免疫反应的关键组成部分。这些先天免疫细胞的数量或功能的紊乱会显著增加侵袭性真菌感染的易感性。每年有数十亿人感染致病性真菌，而这些真菌的临床需求尚未得到满足，许多感染与高死亡率相关，主要影响有潜在免疫缺陷的脆弱患者。脂质代谢越来越被认为显著影响巨噬细胞的功能，特别是在富含脂质的器官（如大脑）中或专门清除死亡细胞（包括肺部的肺泡巨噬细胞）的巨噬细胞中。在这篇综述中，我们概述了巨噬细胞的脂质代谢，并讨论了脂质的再循环和失调如何影响与抗真菌免疫相关的关键巨噬细胞功能，包括吞噬作用、功能极化和炎性体激活。我们专注于真菌病原体，因为这是人类真菌感染死亡的最常见原因，并且已经有几条证据表明脂质代谢在调控 和巨噬细胞相互作用中发挥作用。
