A research team at the University of Pennsylvania’s School of Veterinary Medicine (PennVet) recently identified new therapeutic targets for the tropical disease leishmaniasis, a parasitic disease that can cause painful skin ulcers that can become metastatic after a period of time.
The team’s report said that the immune system’s T cells activate a signaling pathway that leads to chronic inflammation. The researchers found that blocking one of two major parts of this pathway with U.S. Food and Drug Administration-approved drugs led to notable reductions in lesions in animal models.
Their study found that leishmaniasis parasites were less associated with skin damage compared to a malfunction the the body’s immune response when infected with the disease. Specifically, CD8 T cells were found to promote increased disease rather than protect the body from infection as they normally would.
“In earlier work, we found that CD8 T cells lead to inflammation, but what we didn’t know was what was downstream from the CD8 T cells,” Fernanda O. Novais, research associate with PennVet, said. “Here we discover the pathway by which they cause inflammation.”
In addition to the CD8 T cell discovery, the researchers also found that expression levels of the IL-1b gene were elevated in tissue samples of leishmania lesions. This gene encodes a cytokine, a protein that has an important function in cell signaling, and was found to contribute to leishmania-associated tissue damage. By inhibiting the gene with a drug called anakinra, which blocks the IL-1 receptor, the team saw reduced skin pathology in mice models.
“At this point, we have solid evidence in the mouse that blocking these pathways with a couple of different drugs blocks the pathology, and we have data from patients that this pathway is operating in humans,” senior author of the study Phillip Scott said.