Structurally Distinct Membrane Nanotubes between Human Macrophages Support Long-Distance Vesicular Traffic or Surfing of Bacteria

Abstract

We report that two classes of membrane nanotubes between human monocyte-derived macrophages can be distinguished by their cytoskeletal structure and their functional properties. Thin membrane nanotubes contained only F-actin, whereas thicker nanotubes, i.e., those > approximately 0.7 microm in diameter, contained both F-actin and microtubules. Bacteria could be trapped and surf along thin, but not thick, membrane nanotubes toward connected macrophage cell bodies. Once at the cell body, bacteria could then be phagocytosed. The movement of bacteria is aided by a constitutive flow of the nanotube surface because streptavidin-coated beads were similarly able to traffic along nanotubes between surface-biotinylated macrophages. Mitochondria and intracellular vesicles, including late endosomes and lysosomes, could be detected within thick, but not thin, membrane nanotubes. Analysis from kymographs demonstrated that vesicles moved in a stepwise, bidirectional manner at approximately 1 microm/s, consistent with their traffic being mediated by the microtubules found only in thick nanotubes. Vesicular traffic in thick nanotubes and surfing of beads along thin nanotubes were both stopped upon the addition of azide, demonstrating that both processes require ATP. However, microtubule destabilizing agents colchicine or nocodazole abrogated vesicular transport but not the flow of the nanotube surface, confirming that distinct cytoskeletal structures of nanotubes give rise to different functional properties. Thus, membrane nanotubes between macrophages are more complex than unvarying ubiquitous membrane tethers and facilitate several means for distal interactions between immune cells.

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

“…These nanotubes were shown to facilitate the transfer of lipid organelles between cells through actindependent mechanism. Nanotube structures were also reported to connect a wide range of immune cells, such as T cells, B cells, NK cells, and monocytes (24,75). In the event of disassembly of immunological synapse, formation of membrane nanotubes was observed between B cells and NK cells (76).…”

“…Thicker nanotubes are made up of both F-actin and microtubules, whereas thinner ones contain only F-actin. It was shown that nanotubes containing microtubules transport vesicles over long distances, whereas, using a constitutive flow of nanotube surface, bacteria "surf" along nanotubes that lack microtubules (75). Surface transport along thin nanotubes was found to be dependent on ATP but independent of microtubules.…”

How the Internet of cells has biologists buzzing

“…"The crucial thing is deciding what you're going to dig into and investigate. " His team went on to describe different sorts of nanotube, some holding vesicles and mitochondria inside, and others with bacteria 'surfing' the casing 5 .…”

Nanotubes connecting B lymphocytes: High impact of differentiation-dependent lipid composition on their growth and mechanics

“…NTs may provide routes for extensive exchange of information (specific signals) or biomatter between cells. Trafficking of vesicles [10], calcium ions [11], viral proteins [12], bacteria [10], cytoplasmic molecules, organelles, plasma membrane (PM) components or mRNA [9,11] were observed either inside NTs or on their outer surfaces, suggesting involvement of various motor proteins (myosins, dyneins, or kinesins). Such processes can influence cell development, differentiation, effector functions or cell death in both the innate and adaptive immune systems [13].…”