Functional connectivity between immune cells mediated by tunneling nanotubules

Intercellular signals can be transmitted through neuronal synapses or through gap junctions, with the latter mediating transmission of calcium fluxes and small molecules between cells. We show here that a third form of communication between cells can be mediated by tunneling nanotubules (TNT). When myeloid-lineage dendritic cells and monocytes are triggered to flux calcium by chemical or mechanical stimulation, the signal can be propagated within seconds to other cells at distances hundreds of microns away via TNT. A complex and transient network of TNT is seen in live cells, with individual tubules exhibiting substantial variation in length and diameter. In addition to calcium fluxes, microinjected dye tracers can be transferred through these connections. Following TNT-mediated stimulation, spreading of lamellipodia occurs in dendritic cells characteristic of that seen during the phagocytic response to bacteria. These results demonstrate that nonneuronal cells can transmit signals to distant cells through a physically connected network.