Linked in: immunologic membrane nanotube networks

Abstract

Membrane nanotubes, also termed tunneling nanotubes, are F-actin-based structures that can form direct cytoplasmic connections and support rapid communication between distant cells. These nanoscale conduits have been observed in diverse cell types, including immune, neuronal, stromal, cancer, and stem cells. Until recently, little was known about the mechanisms involved in membrane nanotube development in myeloid origin APCs or how membrane nanotube networks support their ability to bridge innate and adaptive immunity. New research has provided insight into the modes of induction and regulation of the immune process of "reticulation" or the development of multicellular membrane nanotube networks in dendritic cells. Preprogramming by acute type 1 inflammatory mediators at their immature stage licenses mature type 1-polarized dendritic cells to reticulate upon subsequent interaction with CD40 ligand-expressing CD4(+) Th cells. Dendritic cell reticulation can support direct antigen transfer for amplification of specific T cell responses and can be positively or negatively regulated by signals from distinct Th cell subsets. Membrane nanotubes not only enhance the ability of immature dendritic cells to sense pathogens and rapidly mobilize nearby antigen-presenting cells in the peripheral tissues but also likely support communication of pathogen-related information from mature migratory dendritic cells to resident dendritic cells in lymph nodes. Therefore, the reticulation process facilitates a coordinated multicellular response for the efficient initiation of cell-mediated adaptive immune responses. Herein, we discuss studies focused on the molecular mechanisms of membrane nanotube formation, structure, and function in the context of immunity and how pathogens, such as HIV-1, may use dendritic cell reticulation to circumvent host defenses.

Mast cell‐neural interactions contribute to pain and itch

“…According to Weng et al, TNTs offer rapid and direct communication to “alarm” other cells . TNTs are F‐actin‐based structures that form cytoplasmic as well as non‐cytoplasmic connections with distant cells in a process called “reticulation.” TNTs are much like filopodia/pseudopodia described above, except that TNTs are non‐adherent and span distances longer than 100 microns. Murine mast cell TNTs were observed first with costimulation of FcεR1 with CCR1 and MIP‐1α .…”

Intercellular transfer of HLA‐G: its potential in cancer immunology

“…However, our understanding of TnTs is in its infancy, and tremendous aspects of TnTs remain to be explored, although TnTs have been investigated in a wide variety of non‐cancer cells and malignant cells . Among them, TnTs have been reported in immune cells such as B cells, T cells, NK cells, dendritic cells and macrophages and in cancer cells of different origin …”

Potential mechanisms of microRNA mobility

“…The latter one describes dynamic, actin‐based cytoplasmic protrusions that connect two cells over long distances of up to several hundred micrometers . Many different cell types were shown to establish TNTs, including stem cells, neural cells, cancer cells and immune cells . The function of TNTs comprise the propagation of calcium flux to regulate cellular physiology, the transmission of antigens in immune cells, and electrical coupling by integration of cx43 proteins .…”