MassIVE MSV000084509

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Bombardier mediates delivery of short-form Bomanins in the Drosophila Toll response

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Description

Toll mediates a robust and effective innate immune response across vertebrates and invertebrates. In Drosophila melanogaster, activation of Toll by systemic infection drives the accumulation of a rich repertoire of immune effectors in hemolymph, including the recently characterized Bomanins as well as the classical antimicrobial peptides (AMPs). Here we report the functional characterization of a Toll-induced hemolymph protein encoded by the bombardier (CG18067) gene. Using the CRISPR-Cas9 system to generate a precise deletion, we found that Bombardier is required for Toll-mediated defense against fungi and Gram-positive bacteria. Assaying cell-free hemolymph from these flies, we found that the Bomanin-dependent candidacidal activity observed in hemolymph is also dependent on Bombardier, but not on the antifungal AMPs Drosomycin and Metchnikowin. Using mass spectrometry, we demonstrated that deletion of Bombardier results in the specific absence of short-form Bomanins from hemolymph. Flies lacking Bombardier also exhibited a defect in pathogen tolerance that we trace to an autoimmune disorder triggered by Toll activation. These results lead us to a model in which the presence of Bombardier in wild-type flies enables the proper folding, secretion, or intermolecular associations of short-form Bomanins, and the absence of Bombardier disrupts one or more of these steps, resulting in defects in both immune resistance and tolerance. [doi:10.25345/C5QX0B] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Drosophila melanogaster, immunity, Toll, Bomanins, humoral, inflammation

Contact

Principal Investigators:
(in alphabetical order) 		Steven A. Wasserman, University of California, San Diego, United States
Submitting User: Amit_Fulzele1803

Publications

Lin SJH, Fulzele A, Cohen LB, Bennett EJ, Wasserman SA.
Bombardier Enables Delivery of Short-Form Bomanins in the Drosophila Toll Response.
Front Immunol. Epub 2020 Jan 10.

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