The new study reveals a new twist in the complex relationship between humans and their associated microbes
Common fungi, often present in the gut, teach the immune system how to respond to their more dangerous relatives, according to new research from scientists at Weill Cornell Medicine. Breakdowns in this process can leave people susceptible to deadly fungal infections. The study, published in the journal Cell points the way toward novel therapies that could help combat a rising tide of drug-resistant pathogens. The discovery stemmed from work on inflammatory bowel disease, which often causes patients to carry larger than normal populations of fungi in their guts. These patients often develop strong antibody responses against mannan, a molecule common to a wide range of fungal species. However, Dr. Iliyan Iliev, associate professor of immunology and microbiology in medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine, noticed that healthy controls in these studies also had some level of anti-fungal antibodies.
The researchers developed a platform that allowed them to determine which gut fungi are targeted by antibodies in the blood of individual patients. They detected a strong response against the yeast Candida albicans. Turning to experiments in mice, Iliev and Itai Doron, a Weill Cornell Medicine Graduate School of Medical Sciences doctoral student in the lab and a first author in the study, found that colonizing the animals’ guts with Candida albicans caused them to develop antibodies against the fungus in their bloodstreams, even though they didn’t develop blood-borne fungal infections. Instead, the animals’ immune cells appeared to transport fungal antigens to the spleen, stimulating the production of circulating antibodies in the bloodstream. “Those fungi just educate that immune response,” Iliev said.
In patients with suppressed immune systems fungi in the gut can invade the bloodstream and cause life-threatening infections. Iliev and his colleagues mimicked this process by treating mice with immunosuppressive drugs. When a Candida species colonizes the gut of these mice, the fungus moves into the bloodstream, causing a fatal infection. Treating the mice with purified anti-fungal antibodies from donor animals protected the immunosuppressed mice from these infections. The same strategy worked against infection with either C. albicans or the emerging pathogenic yeast C. auris.
In patients with suppressed immunity, the anti-fungal antibodies may decline, leaving them vulnerable to fungal infection. New therapies that involve either stimulating the production of anti-fungal antibodies, or injecting such purified antibodies directly into patients’ bloodstreams, could potentially help combat these increasingly common infections.
(Source: Cornell University news release)
