Returning to dendritic cells, they found that by giving a deliberate poke with an empty microinjection tip it caused the same reaction. But why some cells responded and others did not made Drs. Salter and Watkins wonder if there was some sort of physical structure connecting only those cells that discharged. A literature search turned up a handful of papers describing tunneling nanotubules, and further imaging using the highest magnification possible disclosed their presence in both the dendritic cells and macrophages.
In their most definitive experiment, the researchers placed dendritic cells, macrophages and a small amount of the E. coli mixture in the same culture dish. The dendritic cells, as would be expected, fluxed calcium in response to the E. coli. But a few seconds later, calcium could also be seen shooting through the tiny tunnels extending from dendritic cells to neighboring macrophages.
"This may solve some of the mystery of how a local stimulus directed at a very small number of cells can be amplified and result in a successful immune response," explained Dr. Watkins.
"Quite possibly, the tunneling nanotubules enable a small number of dendritic cells with captured antigens to reach other dendritic cells in lymph nodes, increasing the number of these cells capable of stimulating T lymphocytes," added Dr. Salter.
The finding that nanotubules play a role in sending molecular signals to other immune system cells calls into question the long-held belief that immune system cells talk to one another solely by secreting substances such as cytokines, the authors say. It now seems clear that intercellular communication is much more complicated. While it would be fascinating to see this interplay inside living tissue, detecting the tiny tubules in such a complex environment may be nearly impossible with current technology.