A mouse immune cell that plays dual roles as both assassin and messenger, normally the job of two separate cells, has been discovered by an international team of researchers from the United States and France.
The discovery has triggered a race among scientists to find a human equivalent of the multitasking cell, which could one day be a target for therapies that seek out and destroy cancer.
"In the same way that intelligence and law enforcement agencies can face deadly threats together instead of separately, this one cell combines the ability to kill foreign pathogens and distribute information about that experience," says Drew Pardoll, M.D., Ph.D., the Seraph Professor of Oncology at the Johns Hopkins Kimmel Cancer Center.
"We think this hybrid cell speeds up immune reactions and makes the system more efficient," adds Pardoll, whose findings are reported in the February issue of Nature Medicine.
The Hopkins investigators speculate that the hybrid, dubbed "IKDC" for interferon-producing killer dendritic cell, has been missed by cancer biologists because it is rare, making up one-tenth of cells in the spleen with similar features, such as other dendritic cells, according to Frank Housseau, Ph.D., research associate at Hopkins' Kimmel Cancer Center and member of Pardoll's immunology laboratory.
Most of the immune system typically works through a web of cross-talk and signaling among a variety of cells. One of the first immune cells that invading bacteria or cancer cells - both of which carry antigens that alert the immune system - may encounter is a natural killer (NK) cell. As its name implies, NK cells deliver a deadly blow by poking holes in the invader's outer membrane. Then, NK cells secrete molecules that reach other immune cells, including dendritic cells, known as the main messenger for the immune system. Dendritic cells spread "look here" information about foreign invaders to other immune cells, but do not actually kill the invaders.
It was while investigating a particular type of dendritic cell that Housseau noticed the outer membranes of these cells were studded with what were supposed to be hallmarks of NK cells, akin to finding feathers on a dog.
"We thought we were looking at dendritic cells, but we were wrong - they were some type of NK-dendritic cell blend," says Housseau. The blended cell turned out to be a newly identified actor on the immune system stage that retains all the molecular characteristics of both NK and dendritic cells.
Probing further, Housseau scoured the surface of IKDCs to create a sketch of its molecular profile. He found that it produces both types of interferon proteins, normally secreted independently by NK and dendritic cells. He also found both NK and dendriticlike molecules on the surface of IKDCs. Housseau calculated that they account for about 10 percent of conventional dendritic cells in the spleen.
IKDCs begin their lives behaving like an NK cell. After the cell encounters a pathogen, the cell switches roles from killer to dendriticlike messenger, and, according to the researchers, the swap occurs only once. Then, the cell dies and is replenished by the bone marrow.