NIH Funds New Research Into How Our Bodies Fight Fungal Infections

NIH Funds New Research Into How Our Bodies Fight Fungal Infections

A University of Toledo immunologist has received a federal grant to study how a type of cell unexpectedly discovered in the oral cavity helps the body fight off fungal infections.

The cells, called megakaryocytes, are predominantly present in bone marrow, where they produce blood platelets crucial for blood clotting.

Recent research led by Dr. Heather Conti, an associate professor in the College of Natural Sciences and Mathematics, however, found those cells also were present in the tongue - and that they seem to play a key role in the immune system's response to a common but potentially dangerous fungal infection.

"It was a surprising discovery. Others have shown megakaryocytes in the lungs, but no one had previously described them in the oral mucosa," Conti said. "We were seeing that they respond to the fungal infection. They expand and they make things that are involved in clearing that infection. They appear to have an important role."

Those findings, published last year in the journal Mucosal Immunology, form the basis of Conti's new project, which received a three-year $473,632 grant from the National Institute of Dental and Craniofacial Research earlier this spring.

Conti primarily studies oral candidiasis, a condition popularly known as thrush that results from an overgrowth of a yeast called Candida.

Candida is widespread. Up to 80% of people have it on their skin or in their mouth, and for the vast majority it causes no problems.

However, in people with weak or compromised immune systems - including infants and the elderly, as well as those being treated for cancer or autoimmune disorders - the yeast can grow out of control.

"We generally have mechanisms that allow it to live peacefully in our oral cavity and on our skin. But given the opportunity, Candida can make some compounds that are really destructive to human tissue," Conti said. "It can invade tissue, it can enter the blood stream and it can enter different tissue compartments. In the right conditions, it has the potential to be very dangerous."

Conti said up to 40% of disseminated hospital-acquired candidiasis cases, for example, are fatal.

Her NIH-funded project is specifically focused on studying how oral megakaryocytes interact with Candida and with a cytokine called interluken-17, which is a specialized protein that helps regulate the body's immune response.

Though interluken-17 is beneficial in the context of clearing fungal infections, it also is believed to play a significant role in the development of several autoimmune diseases. As such, it and similar cytokines are increasingly being targeted with next-generation inhibitors to alleviate the symptoms of autoimmune disorders like psoriasis.

With autoimmune disorders on the rise - and some species of Candida showing resistance to current antifungal medications - decoding the body's immune response against fungal infections is increasingly important.

"Any time we better understand the immune response against the fungus and how we can take advantage of that, it means less antifungal usage," Conti said. "Those medications are toxic and infections don't always respond. Learning everything we can about our body's own defenses is really important."

While focused specifically on oral fungal infections, Conti's research also has the potential to unlock more secrets about the immune system in general.

"This adds to our knowledge of what interluken-17 is doing in the body," she said. "Even though we've been studying it for a while, we continue to learn new things about it and new cells it can interact with. This is a new cell that interleukin-17 talks to, and we'll be able to understand better what that means not just in the oral cavity, but throughout the body as well."