Fungal infections are major causes of invasive diseases like sepsis and are also involved in mucosal and cutaneous diseases. According to a recent study led by researchers at Baylor College of Medicine, fungal infections can also have an impact on the brain.
The team reported today in Nature Communications the unexpected finding that the common yeast Candida albicans can cross the blood-brain barrier and trigger an inflammatory response that results in the formation of granuloma-type structures and temporary mild memory impairments in mice. Interestingly, the granulomas share features with plaques found in Alzheimer's disease.
"An increasing number of clinical observations by us and other groups indicates that fungi are becoming a more common cause of upper airway allergic diseases such as asthma, as well as other conditions such as sepsis," said corresponding author David B. Corry. "These observations led us to investigate the possibility that fungus might produce a brain infection and, if so, the consequences of having that kind of infection," he added.
The researchers began their investigation by developing a mouse model of a low-grade fungus infection with C. albicans that would not cause severe disease, but might carry implications for brain function. They tested several doses and finally settled on one dose of 25,000 yeasts.
They injected C. albicans into the blood stream of mice and discovered that the yeast can cross the blood-brain barrier. "We thought that yeast would not enter the brain, but it does," Corry said. "In the brain, the yeast triggered the activity of microglia, a resident type of immune cell. The cells became very active 'eating and digesting' the yeast. They also produced a number of molecules that mediated an inflammatory response leading to the capture of the yeasts inside a granule-type structure inside the brain. We called it fungus-induced glial granuloma, or FIGG."
Corry and his colleagues also tested the animals' memory in both yeast-infected and non-infected mice. They found that infected mice had impaired spatial memory, which reversed when the infection cleared.
The mice cleared the yeast infection in about 10 days; however, the microglia remained active and the FIGGs persisted well past this point, out to at least day 21. Intriguingly, as the FIGGs formed, amyloid precursor proteins accumulated within the periphery and amyloid beta molecules built up around yeast cells captured at the center of FIGGs. These amyloid molecules are typically found in plaques that are the trademark of Alzheimer's disease.
"These findings suggest that the role fungi play in human illness potentially goes well beyond allergic airway disease or sepsis," Corry said. "The results prompted us to consider the possibility that in some cases, fungi also could be involved in the development of chronic neurodegenerative disorders, such as Alzheimer's, Parkinson's, and multiple sclerosis. We are currently exploring this possibility."