Fountain Aaron, Inpanathan Subothan, Alves Patris, Verdawala Munira B, Botelho Roberto J
Department of Chemistry and Biology and Graduate Program in Molecular Science, Ryerson University, Toronto, Ontario, M5B2K3, Canada; Graduate Program in Molecular Science, Ryerson University, Toronto, Ontario, M5B2K3, Canada.
Department of Chemistry and Biology and Graduate Program in Molecular Science, Ryerson University, Toronto, Ontario, M5B2K3, Canada.
Adv Biol Regul. 2021 Dec;82:100832. doi: 10.1016/j.jbior.2021.100832. Epub 2021 Oct 8.
Phagocytosis is a dynamic process that requires an intricate interplay between phagocytic receptors, membrane lipids, and numerous signalling proteins and their effectors, to coordinate the engulfment of a bound particle. These particles are diverse in their physico-chemical properties such as size and shape and include bacteria, fungi, apoptotic cells, living tumour cells, and abiotic particles. Once engulfed, these particles are enclosed within a phagosome, which undergoes a striking transformation referred to as phagosome maturation, which will ultimately lead to the processing and degradation of the enclosed particulate. In this review, we focus on recent advancements in phagosome maturation in macrophages, highlighting new discoveries and emerging themes. Such advancements include identification of new GTPases and their effectors and the intricate spatio-temporal dynamics of phosphoinositides in governing phagosome maturation. We then explore phagosome fission and recycling, the emerging role of membrane contact sites, and delve into mechanisms of phagosome resolution to recycle and reform lysosomes. We further illustrate how phagosome maturation is context-dependent, subject to the type of particle, phagocytic receptors, the phagocytes and their state of activation during phagocytosis. Lastly, we discuss how phagosomes serve as signalling platforms to help phagocytes adapt to their environmental conditions. Overall, this review aims to cover recent findings, identify emerging themes, and highlight current challenges and directions to improve our understanding of phagosome maturation in macrophages.
吞噬作用是一个动态过程，需要吞噬受体、膜脂以及众多信号蛋白及其效应器之间复杂的相互作用，以协调对结合颗粒的吞噬。这些颗粒在物理化学性质上各不相同，如大小和形状，包括细菌、真菌、凋亡细胞、活肿瘤细胞和非生物颗粒。一旦被吞噬，这些颗粒就被包裹在吞噬小体内，吞噬小体会经历一种显著的转变，称为吞噬小体成熟，这最终将导致被包裹颗粒的加工和降解。在这篇综述中，我们聚焦于巨噬细胞吞噬小体成熟的最新进展，突出新的发现和新出现的主题。这些进展包括新的GTP酶及其效应器的鉴定，以及磷酸肌醇在控制吞噬小体成熟过程中复杂的时空动态变化。然后，我们探讨吞噬小体的分裂和再循环、膜接触位点的新作用，并深入研究吞噬小体分解以再循环和重塑溶酶体的机制。我们还进一步阐述了吞噬小体成熟如何依赖于具体情况，取决于颗粒的类型、吞噬受体、吞噬细胞及其在吞噬过程中的激活状态。最后，我们讨论吞噬小体如何作为信号平台帮助吞噬细胞适应其环境条件。总的来说，这篇综述旨在涵盖最近的研究发现，确定新出现的主题，并突出当前的挑战和方向，以增进我们对巨噬细胞吞噬小体成熟的理解。
