When a pathogenic bacteria or fungus approaches us, we produce antimicrobial peptides to combat infection, so that we can continue to stay healthy and thrive. How does the pathogen perceive their interaction with us? Do pathogens combat our defences so that they can survive, or further, are we a good meal to them?
Fungi evolve within the host, ensuring their own nutrition and reproduction, at the expense of host health. They intervene in hosts’ brain function, to alter host behaviour and induce neurodegeneration. In humans, fungal infections are emerging as drivers of neuroinflammation, neurodegenerative diseases and psychiatric disorders. However, how fungi alter the host brain is unknown. Fungi trigger an innate immune response mediated by the Toll-1/TLR receptors, the adaptor MyD88 and the transcription factors Dif/NFκB, that induce the expression of antimicrobial peptides (AMPs). However, in the nervous system, Toll-1/TLR could also drive an alternative pathway involving the adaptor Sarm, which causes cell death instead. Sarm is the universal inhibitor of MyD88 and could drive immune evasion. The entomopathogenic fungus Beauveria bassiana is well-known to activate Toll-1 signalling in innate immunity in Drosophila. Furthermore, in fruit-flies, the adaptor Wek links Toll-1 to Sarm. Thus, here we asked whether B. bassiana could damage the Drosophila brain via Toll-1, Wek and Sarm. Our data show that B. bassiana causes cell loss in the host brain via Toll-1/Wek/Sarm signalling driving immune evasion. We conclude that pathogens can benefit from an innate immunity receptor to damage the host brain. A similar activation of Sarm downstream of TLRs in response to fungal infections could underlie psychiatric and neurodegenerative diseases in humans.
Find out more here: DOI https://doi.org/10.1101/2024.04.29.591341