Phagosome maturation in macrophages: Eat, digest, adapt, and repeat

Abstract

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.

Keywords: Adaptation; Immunity; Membrane; Organelles; Phagocytosis; Signalling.