Swollen lymph nodes are an all-too-familiar discomfort during cold and flu season. The swelling is a key event in the immune response, but what triggers it is poorly understood. Now a research team thinks they've figured it out. The credit may bolster the reputation of an immune cell that's so far received mainly unflattering press.
Once a bacterial infection is detected, it is only a matter of hours before the lymph nodes begin to swell with T cells, the main soldiers of the immune system. Soman Abraham, an immunologist at Duke University Medical Center in Durham, North Carolina, suspected that certain immune cells, called mast cells, might be involved. Mast cells are best known for what they do wrong: Overactive mast cells contribute to allergic reactions and other immune system flare-ups. But the cells also hang out in the skin and mucosa where infections usually occur, and they carry packages of signaling molecules that can be dumped into the bloodstream to activate local immune reactions.
To test whether the mast cells are responsible for lymph node swelling, Abraham and colleagues injected bacteria under the skin of mutant mice that have no mast cells. Sure enough, the lymph nodes of mice devoid of mast cells remained small after infection. But when these mice were injected with a supply of mast cells, their lymph nodes puffed right up. Next, Abraham's team tested the various signaling molecules that mast cells pack. One of these, tumor necrosis factor, was able to induce node swelling all on its own, the team reports in the 2 November issue of Nature Immunology. "Mast cells have been much maligned as a result of their contribution to diseases including asthma, arthritis, Crohn's disease, and multiple sclerosis," says Abraham, but the discovery that a single molecule they produce triggers the immune system to fight infection shows that mast cells play a "critical physiological role."
But don't blame your painful nodes on mast cells just yet. Jean Marshall, an immunologist at Dalhousie University in Halifax, Canada, cautions that these experiments only show that mast cells in the skin, where the bacteria were injected, can cause lymph nodes to swell. Similar experiments are needed to show that mast cells in the mucosa, where most infectious agents are first encountered, also cause swelling, she says. "The relative role of mast cells may differ substantially from tissue to tissue."