Abstract
Macrophages internalize pathogens for intracellular degradation. An important part of this process is the phagosomal transport from the cell periphery to the perinuclear region. Biochemical factors are known to influence the fate of phagosomes. Here, we show that the size of phagosomes also has a strong influence on their transport. We found that large phagosomes are transported persistently to the nucleus, whereas small phagosomes show strong bidirectional transport. We show that dynein motors play a larger role in the transport of large phagosomes, whereas actin filament-based motility plays a larger role in the transport of small phagosomes. Furthermore, we investigated the spatial distribution of dyneins and microtubules around phagosomes and hypothesize that dynein and microtubule density differences between the nucleus-facing side of phagosomes and the opposite side could explain part of the observed transport characteristics. Our findings suggest that a size-dependent cellular sorting mechanism might exist that supports macrophages in their immunological roles.
Highlights
The internalization of pathogens by macrophage phagocytosis and the subsequent digestion of pathogens within the macrophages are two of the key processes of the mammalian immune system[1]
Since the transport of a phagosome to the perinuclear region is an important part of the maturation process[10,11,12,13], we investigate in this work the influence of phagosome size on the phagosomal transport behavior
To test whether the potentially missing first segments of the phagosomal tracks have an influence on the determined phagosomal transport characteristics, we performed additional experiments with full control over the starting time point of phagocytosis
Summary
The internalization of pathogens by macrophage phagocytosis and the subsequent digestion of pathogens within the macrophages are two of the key processes of the mammalian immune system[1]. Many bacteria can interrupt the phagocytic maturation process to prevent their digestion and can even replicate within the macrophages themselves[2,3,4,5]. Common examples for such bacteria include Mycobacterium spp., Salmonella spp., Cryptococcus neoformans, Chlamydia spp. or Brucella abortus; the first two types of bacteria can arrest phagosome maturation and the latter two examples can convert a phagosome into a non-phagosomal organelle[2,6,7]. Several studies have investigated the influence of the phagocytic target size on the engulfment process in macrophages[14,15,16,17], but its influence on subsequent phagosome transport is still largely unknown, aside from the finding that phagosome size has an influence on lysosome delivery[14]. Direction changes during transport can be associated with specific cellular functions, such as the removal of phagocytic remnants for antigen presentation at the end of a successful phagosome maturation[11,24,25,26]
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