With the unusual opportunity that human leprosy infections provide for study of human immune responses, scientists have discovered how the body's early warning system prompts a rapid immune response by two separate armies of defensive cells.
The finding helps explain why, when threatened by microbes like the leprosy bug, this initial defense sometimes succeeds in limiting the damage, but in other cases yields to a dangerous, spreading infection.
Led by Stephan R. Krutzik of UCLA, a team of scientists that includes Barry R. Bloom, Dean of the Harvard School of Public Health, reported the work on May 8 in an advance online publication of Nature Medicine.
The researchers isolated immune cells in blood samples from healthy people and exposed the cells to a component of mycobacteria. The large white blood cells known as monocytes rapidly differentiated into the two distinct cell types, forming the body's emergency response to the detection of foreign bacteria. One category of defensive cells, macrophages, seek out and engulf the infectious bugs. The other group consists of dendritic, or "antigen-presenting" cells, which seize distinctive pieces of the enemy and use them to "educate" and stir up a second immune response, known as "adaptive" immunity.
Until now, laboratory dish experiments hadn't revealed that the instantaneous or "innate" immune reaction-discovered less than 10 years ago-is mounted by two differently-specialized cells. It had been thought that the initially responding cells were uniformly macrophages, equipped for the two roles. The innate response swings into action when invading microbes are detected by molecules called Toll-like receptors (TLRs) that stick out of the cell's outer membrane, serving as a trip-wire to raise the alarm. The TLRs spur the monocytes to differentiate into the two rapid response cell types.