The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins. (2nd November 2022)

• Record Type: Journal Article
• Authors: Xu, Rui; Lou, Yanyan; Tidu, Antonin; Bulet, Philippe; Heinekamp, Thorsten; Martin, Franck; Brakhage, Axel; Li, Zi; Liégeois, Samuel; Ferrandon, Dominique
• Is Part Of: EMBO reports. Volume 24:Number 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-02
• Subjects: Drosophila melanogaster -- fumitremorgin/verruculogen -- fungal infections -- resilience/disease tolerance -- restrictocin; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.202256036
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: Host defense against infections encompasses both resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, which allows the host to withstand/tolerate pathogens and repair damages. In Drosophila, the Toll signaling pathway is thought to mediate resistance against fungal infections by regulating the secretion of antimicrobial peptides, potentially including Bomanins. We find that Aspergillus fumigatus kills Drosophila Toll pathway mutants without invasion because its dissemination is blocked by melanization, suggesting a role for Toll in host defense distinct from resistance. We report that mutants affecting the Toll pathway or the 55C Bomanin locus are susceptible to the injection of two Aspergillus mycotoxins, restrictocin and verruculogen. The vulnerability of 55C deletion mutants to these mycotoxins is rescued by the overexpression of Bomanins specific to each challenge. Mechanistically, flies in which BomS6 is expressed in the nervous system exhibit an enhanced recovery from the tremors induced by injected verruculogen and display improved survival. Thus, innate immunity also protects the host against the action of microbial toxins through secreted peptides and thereby increases its resilience to infection. Synopsis: Toll signaling is thought to mediate fungal resistance by regulating the secretion of antimicrobial peptides. This study shows that Toll signaling is not needed to prevent Aspergillus fumigatus invasion but protects Drosophila against specific mycotoxins. Melanization but not the Toll pathway prevents the proliferation and dissemination of A. fumigatus in flies. Toll mutant flies succumb to A. fumigatus secreted mycotoxins restrictocin and verruculogen. Specific Bomanins as well as other Toll targets prevent restrictocin from efficiently cleaving its 28S RNA substrate. BomS6 expressed in the brain mediates fast recovery from toxic effects of verruculogen and thereby protects the host. Abstract : Toll signaling is thought to mediate fungal resistance by regulating the secretion of antimicrobial peptides. This study shows that Toll signaling is not needed to prevent Aspergillus fumigatus invasion but protects Drosophila against specific mycotoxins.