A fungus that is killing frogs and other amphibians around the world releases a toxic factor that disables the amphibian immune response, Vanderbilt University investigators reported in the journal Science.
The findings represent “a step forward in understanding a long-standing puzzle — why the amphibian immune system seems to be so inept at clearing the fungus,” said Louise Rollins-Smith, associate professor of pathology, microbiology and immunology. Although the identity of the toxic fungal factor or factors remains a mystery, its ability to inhibit a wide range of cell types — including cancerous cells — suggests that it may offer new directions for the development of immunosuppressive or anti-cancer agents.
The populations of amphibian species have been declining worldwide for more than 40 years. In the late 1990s, researchers discovered that an ancient fungus, Batrachochytrium dendrobatidis,was causing skin infections, and the fungus is now recognized as a leading contributor to global amphibian decline.
Ms. Rollins-Smith, an immunologist, and her colleagues have been studying the immune response to the fungus for more than 10 years.
“Amphibians have excellent and complex immune systems, nearly as complex as humans, and they should be able to recognize and clear the fungus,” she said.
In early studies, the investigators demonstrated that some frogs produce anti-microbial peptides in the skin that offer a first layer of defense against the fungus. But when the fungus gets into the layers of the skin, Ms. Rollins-Smith said, the conventional immune response, lymphocytes, should be activated to clear it.
“We think it’s not a block at the initial recognition stage,” Rollins-Smith said. “The macrophages and neutrophils can see it as a pathogen, they can eat it up, they can do their thing.”
But during the next stage of the immune response, when lymphocytes should be activated, the fungus exerts its toxic effects. The investigators demonstrated that B. dendrobatidiscells and the incubation liquid separated from the cells impaired lymphocyte proliferation and induced cell death of lymphocytes from frogs, mice and humans. The toxic fungal factor also inhibited the growth of cancerous mammalian cell lines.
“Fungal infection causes rapid behavioral changes — frogs become lethargic and start to crawl out of the water — suggesting that even though the fungus stays in the skin, the toxic material is having effects elsewhere,” the researcher said.