RRC ID 48864
著者 Aittomäki S, Valanne S, Lehtinen T, Matikainen S, Nyman TA, Rämet M, Pesu M.
タイトル Proprotein convertase Furin1 expression in the Drosophila fat body is essential for a normal antimicrobial peptide response and bacterial host defense.
ジャーナル FASEB J
Abstract 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 fat body. 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.
巻・号 31(11)
ページ 4770-4782
公開日 2017-11-1
DOI 10.1096/fj.201700296R
PII fj.201700296R
PMID 28705811
MeSH Animals Antimicrobial Cationic Peptides / genetics Antimicrobial Cationic Peptides / immunology Antimicrobial Cationic Peptides / metabolism* Drosophila Proteins / biosynthesis* Drosophila Proteins / genetics Drosophila Proteins / immunology Drosophila melanogaster Furin / biosynthesis* Furin / genetics Furin / immunology Gene Expression Regulation, Enzymologic* Gram-Negative Bacteria / immunology Gram-Negative Bacteria / metabolism Gram-Negative Bacterial Infections / enzymology Gram-Negative Bacterial Infections / genetics Gram-Negative Bacterial Infections / immunology Gram-Positive Bacteria / immunology Gram-Positive Bacteria / metabolism Gram-Positive Bacterial Infections / enzymology Gram-Positive Bacterial Infections / genetics Gram-Positive Bacterial Infections / immunology
IF 4.966
引用数 3
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