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Proprotein convertase Furin1 expression in the Drosophila fat body is essential for a normal antimicrobial peptide response and bacterial host defense
Author(s) -
Aittomäki Saara,
Valanne Susanna,
Lehtinen Tapio,
Matikainen Sampsa,
Nyman Tuula A.,
Rämet Mika,
Pesu Marko
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700296r
Subject(s) - biology , antimicrobial peptides , innate immune system , proprotein convertase , cecropin , immune system , rna interference , drosophila melanogaster , microbiology and biotechnology , signal transduction , gene silencing , proprotein convertases , immunology , antimicrobial , gene , genetics , rna , biochemistry , cholesterol , lipoprotein , ldl receptor
Invading pathogens provoke robust innate immune responses in Dipteran insects, such as Drosophila melanogaster. In a systemic bacterial infection, a humoral response is induced in the fatbody. Gram‐positive bacteria trigger the Toll signaling pathway, whereas gram‐negative bacterial infections are signaled via the immune deficiency (IMD) pathway. We show here that the RNA interference‐mediated silencing of Furin1 —a member of the proprotein convertase enzyme family—specifically in the fat body, results in a reduction in the expression of antimicrobial peptides. This, in turn, compromises the survival of adult fruit flies in systemic infections that are caused by both gram‐positive and ‐negative bacteria. Furin1 plays a nonredundant role in the regulation of immune responses, as silencing of Furin2 , the other member of the enzyme family, had no effect on survival or the expression of antimicrobial peptides upon a systemic infection. Furin1 does not directly affect the Toll or IMD signaling pathways, but the reduced expression of Furin1 up‐regulates stress response factors in the fat body. We also demonstrate that Furin1 is a negative regulator of the Janus kinase/signal transducer and activator of transcription signaling pathway, which is implicated in stress responses in the fly. In summary, our data identify Furin1 as a novel regulator of humoral immunity and cellular stress responses in Drosophila. —Aittomäki, S., Valanne, S., Lehtinen, T., Matikainen, S., Nyman, T. A., Rämet, M., Pesu, M. Proprotein convertase Furin1 expression in the Drosophila fat body is essential for a normal antimicrobial peptide response and bacterial host defense. FASEB J. 31, 4770–4782 (2017). www.fasebj.org