Toll-1-dependent immune evasion induced by fungal infection leads to cell loss in the Drosophila brain

• DOI: 10.1371/journal.pbio.3003020
• Publication Date: 2025-02-13T18:52:48Z
• Authors: Deepanshu N. D. S...; Abigail R. E. Rob...; Xiaocui Wang; Guiyi Li; Enrique Quesada M...; David Alliband; Elizabeth Ballou; Hung-Ji Tsai; Alicia Hidalgo
• Keywords: QH301-705.5; Biology (General)

Fungi can intervene in hosts’ brain function. In humans, they drive neuroinflammation, neurodegenerative diseases and psychiatric disorders. However, how fungi alter the host is unknown. The mechanism underlying innate immunity to well-known universally conserved downstream of shared Toll/TLR receptors, which via adaptor MyD88 transcription factor Dif/NFκB, induce expression antimicrobial peptides (AMPs). brain, Toll-1 could also an alternative pathway Sarm, causes cell death instead. Sarm universal inhibitor immune evasion. Here, we show that exposure fungus Beauveria bassiana reduced fly life span, impaired locomotion caused neurodegeneration. entered Drosophila induced up-regulation AMPs , Toll adaptors wek sarm within brain. RNAi knockdown Toll-1, or concomitantly with infection prevented B. bassiana- loss. By contrast, over-expression was sufficient cause neuronal loss absence infection. Thus, Toll-1/Wek/Sarm signalling driving A similar activation TLRs upon fungal infections underlie humans.