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Updated: Aug 23, 2025
Assessing the Cellular Immune Response of the Fruit Fly, Drosophila melanogaster, Using an In Vivo Phagocytosis Assay
Published on: April 10, 2019
The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins
Rui Xu1,2,3, Yanyan Lou1,2,3, Antonin Tidu2,4
1Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, China.
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.
Insights
Host defense involves resistance and resilience. Drosophila Toll pathway and Bomanins protect against Aspergillus fumigatus toxins, enhancing host resilience to infection.
Area of Science:
- Immunology
- Infectious Diseases
- Toxicology
Background:
- Host defense mechanisms include resistance and resilience.
- The Toll signaling pathway in Drosophila is linked to antimicrobial peptide secretion and fungal resistance.
- Aspergillus fumigatus poses a threat through both infection and mycotoxin production.
Purpose of the Study:
- To investigate the role of the Drosophila Toll pathway and Bomanins in host defense against Aspergillus fumigatus.
- To determine if Toll pathway and Bomanins confer resilience against fungal mycotoxins.
- To elucidate the mechanism by which Bomanins provide protection against mycotoxins.
Main Methods:
- Utilizing Drosophila mutants in the Toll pathway and Bomanin locus.
- Challenging flies with Aspergillus fumigatus and its mycotoxins (restrictocin, verruculogen).
- Assessing survival rates and employing genetic manipulation (overexpression) to study rescue effects.
Main Results:
- Toll pathway mutants exhibit susceptibility to mycotoxins, independent of fungal invasion.
- Bomanin locus mutants are vulnerable to restrictocin and verruculogen.
- Overexpression of specific Bomanins rescues mycotoxin susceptibility.
- BomS6 expression in the nervous system enhances recovery and survival from verruculogen exposure.
Conclusions:
- The Toll pathway and Bomanins contribute to host resilience by neutralizing mycotoxins.
- Innate immunity provides protection against microbial toxins, increasing host tolerance to infection.
- Secreted peptides play a crucial role in mitigating toxin-induced damage and enhancing host survival.
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