Infection Fighter Found

University of Maryland researchers have discovered a mechanism that allows cells in the liver to capture potentially fatal fungi in the bloodstream before they target organs like the brain or kidneys—a finding that could explain liver disease patients’ increased susceptibility to fungal infections, while pointing to therapeutic options for ailments that kill 1.5 million people annually.

In a paper published yesterday in Nature Communications, Meiqing Shi, associate professor with the Department of Veterinary Medicine, shows how a kind of macrophage, or white blood cell known as a Kupffer cell (KC), captures fungal cells.

Shi’s lab is widely known for its use of intravital microscopy, which allows high-resolution views of biological process inside living organisms to monitor the progression of fungal infections.

“Under intravital microscopy, we can directly see how the KCs catch fungi in real time,” Shi said. “This is a protective mechanism that is working once the fungus becomes invasive, or gets into the bloodstream, to prevent it from spreading. Stopping the dissemination processes throughout the body is so important, because once you get dissemination, you get the disease.”

Shi examined how the liver handles two types of fungi: Cryptococcus neoformans and Candida albicans. Both cause potentially fatal infections in their target organs—the brain for Cryptococcus (the main cause of meningitis) and the kidney for Candida.  

Both are common, and while healthy people can usually overcome infections, those with impaired immune systems, like HIV patients or organ transplant patients, are at increased risk. Patients with liver disease are also more prone to Cryptococcus infection—a mystery until Shi’s discovery that KCs, or liver macrophages, are responsible for catching free fungi in the bloodstream.

“This finding is very interesting and very unusual, because in the field of fungal infections, nobody focuses on the liver,” he said. “Researchers tend to look at the target organs like the brain or kidney. The liver is not a target organ, but it tries to clean out the fungus in the bloodstream. As the whole body is connected, this paper gives a more whole-system approach to how fungal dissemination interacts in the entire body.”

With this whole-body approach in mind, the discovery of this mechanism has implications not just for those with liver disease, but for the treatment of fungal infections generally, which affect more than 1.2 billion people around the world each year.