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Bombardier Enables Delivery of Short-Form Bomanins in the Drosophila Toll Response.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Jan 10; Vol. 10, pp. 3040. Date of Electronic Publication: 2020 Jan 10 (Print Publication: 2019). - Publication Year :
- 2020
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Abstract
- 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 of the bombardier transcriptional unit, we found that Bombardier is required for Toll-mediated defense against fungi and Gram-positive bacteria. Assaying cell-free hemolymph, we found that the Bomanin-dependent candidacidal activity is also dependent on Bombardier, but is independent of 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. In addition, flies lacking Bombardier exhibited a defect in pathogen tolerance that we trace to an aberrant condition 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.<br /> (Copyright © 2020 Lin, Fulzele, Cohen, Bennett and Wasserman.)
- Subjects :
- Animals
Antimicrobial Cationic Peptides immunology
Antimicrobial Cationic Peptides metabolism
Drosophila Proteins immunology
Drosophila melanogaster immunology
Fungi immunology
Gram-Positive Bacteria immunology
Hemolymph immunology
Immunity, Innate immunology
Signal Transduction immunology
Toll-Like Receptors immunology
Drosophila Proteins metabolism
Drosophila melanogaster metabolism
Toll-Like Receptors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 31998316
- Full Text :
- https://doi.org/10.3389/fimmu.2019.03040