Early Interactions of Borrelia Burgdorferi with Immune Cells Resident in Skin
R. Mark Wooten, Ph.D.
University of Toledo, Toledo, OH
David Mahoney Neuroimaging Program
December 2007, for 3 years
Cellular Imaging May Reveal Why Immune Cells in Skin Fail to Respond Effectively in Lyme Disease
Researchers will use multi-photon cellular imaging in a mouse model to determine why immune cells in the skin fail to eliminate the bacterium that causes Lyme disease.
Lyme disease can produce debilitating brain encephalitis and meningitis, peripheral nerve disease, and arthritic joints. It is caused by a bacterium carried by infected ticks; when they bite humans or susceptible animals, the bacterium is transmitted to the skin. Following a bite by an infected tick, the bacteria remain in the skin for at least 24 to 48 hours and then disseminate to the central and peripheral nervous system, and joints. The bacterial membranes contain numerous lipoproteins (a mixture of fats and proteins that transport fats through the body). The lipoproteins elicit responses by three types of immune cells in the skin—dendritic cells, macrophages, and Langerhan cells—but their responses fail to clear the bacteria, allowing the infection to spread. Yet these immune cells do actively pursue the bacteria in laboratory tissue cultures. Studying how the immune response fails to clear the bacteria from the skin, therefore, requires examining it in living skin tissues.
For this reason, the investigators, will directly visualize the interactions between these three types of skin immune cells and the bacterium in infected, anesthetized mice, over time, using intravital multi-photon laser scanning microscopy. They hypothesize that the bacterium’s interactions with the immune macrophages and dendritic cells (but not the Langerhan cells) in the animal leads to the production of pro-inflammatory processes that are capable of promoting an effective response, but that this interaction also elicits a raid and significant increase of an immune cytokine, called IL-10, that suppresses the immune response. They will determine if this is the case by viewing the immune-bacterial interactions in specially engineered mice in which the immune cells fluoresce (glow) green, while the bacterium will glow red.
Significance: If the investigators learn how the Lyme disease bacteria escape immune clearance from the skin, the findings may lead to new methods for prevention or treatment.