ÌÇÐÄÊÓƵ

Fungus 'hacks' natural immune system to cause neurodegeneration in fruit flies

A fungal infection has been shown to trigger a fruit fly's own immune system to destroy brain cells, leading to signs of neurodegeneration, a new study has found.

The paper published in PLOS Biology found that a fungus called Beauveria bassiana was able to make the fly's innate immune system trigger a process that kills neurons and glia in the brain, leading to more than half of flies dying after seven days compared to half of control samples living for nearly 50 days.

In experiments conducted by a team of academics from the University of Birmingham, fruit flies were exposed to B. bassiana in infection chambers. After three days' exposure, the fungus had penetrated the blood-brain barrier and had made its way into the central brain.

The scientists found that the fungus is able to trick the fly's immune system agents called Toll receptors to release two different responses. The Toll-1 receptor triggered the release of antimicrobial peptides (AMPs) as expected, which attack and try to kill pathogens.

However, the fungus also provoked Toll-1 to trigger the production of another molecule called Sarm, which suppresses the immune response and kills brain cells instead.

Alicia Hidalgo, Professor of Neurogenetics at the University of Birmingham and corresponding author of the study said, "We have shown a process for how fungi have evolved to trick the immune system to get into the brain. The fungus is detected by the receptor that does a normal process to induce innate immunity, but in the brain this can also trigger an immune-evasion pathway that induces cell death in the host brain instead.

"The key antagonist in the immune process is Sarm, a so-called master of destruction, that is causing cell death in the brain. The ability of B. bassiana to trick the fruit fly immune system into activating the master of destruction Sarm and kill cells enables spores to beat the blood-brain barrier and start feeding on brain cells."

Dr. Deepanshu Singh, who worked on the study for a Ph.D. carried out at the University of Birmingham, and is now a post-doc at the University of Manchester, said, "From an evolutionary perspective, these findings highlight the ongoing arms race between hosts and pathogens, where hosts enhance their immune mechanisms while pathogens evolve new strategies to evade immunity.

"It is important to stress that B. bassiana cannot affect humans. Some fungi have co-evolved with the host, so they will infect only particular hosts. B. bassiana infects multiple insect species, but not mammals. However, in principle, this study shows that other fungal infections could affect the human brain in analogous ways."