Researchers report that the fungus 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. They have also found Amyloid precursor proteins which are typically present in the plaques of Alzheimer's disease.
A team of researchers at Baylor College of Medicine has developed a mouse model to study the short-term consequences of fungal infection in the brain and they report in the journal Nature Communications the unexpected finding that the common yeast, Candida albicans, can cross the blood-brain barrier and trigger an inflammatory response.
It 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, supporting future studies on the long-term neurological consequences of sustained C. albicans infection.
"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, a potentially life-threatening disease caused by the body's response to an infection," said Dr. David B. Corry.
They tested several doses and finally settled on one dose of 25,000 which they injected into the bloodstream of mice and were surprised to discover that the yeast can cross the blood-brain barrier, a robust protective mechanism the brain employs to exclude all kinds of large and small molecules, as well as a number of microorganisms that can potentially damage the brain.
Fungi's role goes well beyond sepsis
"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 & 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.
"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."
For these reasons, the better understanding of how immune system deals with this kind of constant threat and what are the weaknesses in the immunological Armor that occur with aging that allow the fungal disease to take root would increase the possibility of finding ways to fight back.