Single-phagosome imaging reveals that homotypic fusion impairs phagosome degradative function

Immune cells degrade internalized pathogens in vesicle compartments called phagosomes. Many intracellular bacteria induce homotypic phagosome fusion to survive in host cells, but the fusion interaction between phagosomes and its consequence for phagosome function have scarcely been studied. Here, we characterize homotypic fusion between phagosomes in macrophages and identify how such interactions impact the degradative capacity of phagosomes. By developing a series of particle sensors for measuring biochemical changes of single phagosomes, we show that phagosomes undergo stable fusion, transient kiss-and-runfusion, or both in succession. Super-resolution three-dimensional fluorescence microscopy revealed that stably fused phagosomes are connected by membrane neckswith submicron-sized fusion pores. Furthermore, we demonstrate that, after stable fusion, phagosomes have leaky membranes and thereby impaired degradative functions. Our findings, based on phagosomes that contain synthetic particles, illustrate that homotypic fusion is not exclusive to phagosomes that encapsulate pathogens, as previously believed. The physical process of homotypic fusion is alone sufficient to perturb the degradative functions of phagosomes.

Automated summary

This study characterizes the homotypic fusion between phagosomes in macrophages and explores how this interaction affects the degradative capacity of phagosomes. The researchers found that phagosomes can undergo stable fusion, transient kiss-and-run fusion, or both in succession. Furthermore, they discovered that stable fusion results in leaky membranes and impaired degradative functions in phagosomes.