2025-02-14 バーミンガム大学
<関連情報>
- https://www.birmingham.ac.uk/news/2025/fungus-hacks-natural-immune-system-causing-neurodegeneration-in-fruit-flies
- https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003020
真菌感染によって誘導されるToll-1依存性免疫回避がショウジョウバエの脳で細胞損失を引き起こす Toll-1-dependent immune evasion induced by fungal infection leads to cell loss in the Drosophila brain
Deepanshu N. D. Singh,Abigail R. E. Roberts,Xiaocui Wang,Guiyi Li,Enrique Quesada Moraga,David Alliband,Elizabeth Ballou,Hung-Ji Tsai,Alicia Hidalgo
PLOS Biology Published: February 13, 2025
DOI:https://doi.org/10.1371/journal.pbio.3003020
Abstract
Fungi can intervene in hosts’ brain function. In humans, they can drive neuroinflammation, neurodegenerative diseases and psychiatric disorders. However, how fungi alter the host brain is unknown. The mechanism underlying innate immunity to fungi is well-known and universally conserved downstream of shared Toll/TLR receptors, which via the adaptor MyD88 and the transcription factor Dif/NFκB, induce the expression of antimicrobial peptides (AMPs). However, in the brain, Toll-1 could also drive an alternative pathway via Sarm, which causes cell death instead. Sarm is the universal inhibitor of MyD88 and could drive immune evasion. Here, we show that exposure to the fungus Beauveria bassiana reduced fly life span, impaired locomotion and caused neurodegeneration. Beauveria bassiana entered the Drosophila brain and induced the up-regulation of AMPs, and the Toll adaptors wek and sarm, within the brain. RNAi knockdown of Toll-1, wek or sarm concomitantly with infection prevented B. bassiana-induced cell loss. By contrast, over-expression of wek or sarm was sufficient to cause neuronal loss in the absence of infection. Thus, B. bassiana caused cell loss in the host brain via Toll-1/Wek/Sarm signalling driving immune evasion. A similar activation of Sarm downstream of TLRs upon fungal infections could underlie psychiatric and neurodegenerative diseases in humans.
