Antimicrobial peptide defense in <i>Drosophila</i>

Meister, Marie; Lemaître, Bruno; Hoffmann, Jules A.

doi:10.1002/bies.950191112

Cited by 164 publications

(54 citation statements)

References 85 publications

(27 reference statements)

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“…The presence of potential binding sites for liver-enriched transcription factors C/EBP␤ (62,63) and HNF3␤ (64), known to regulate expression of several hepatic genes, indicates that these transcription regulators could confer liver specificity to hepcidin. To our knowledge, it is the first demonstration of a liver-specific mammalian antimicrobial peptide that is reminiscent of insect antimicrobial peptides in the fat body, the functional equivalent of mammalian liver (65,66). However, we did not find any structural homologues of mammalian prohepcidin in the Drosophila genome.…”

Section: Discussioncontrasting

confidence: 56%

A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload

Pigeon

Ilyin

Courselaud

et al. 2001

Journal of Biological Chemistry

1,506

1,264

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Considering that the development of hepatic lesions related to iron overload diseases might be a result of abnormally expressed hepatic genes, we searched for new genes up-regulated under the condition of iron excess. By suppressive subtractive hybridization performed between livers from carbonyl iron-overloaded and control mice, we isolated a 225-base pair cDNA. By Northern blot analysis, the corresponding mRNA was confirmed to be overexpressed in livers of experimentally (carbonyl iron and iron-dextran-treated mice) and spontaneously (␤ 2 -microglobulin knockout mice) ironoverloaded mice. In addition, ␤ 2 -microglobulin knockout mice fed with a low iron content diet exhibited a decrease of hepatic mRNA expression. The murine fulllength cDNA was isolated and was found to encode an 83-amino acid protein presenting a strong homology in its C-terminal region to the human antimicrobial peptide hepcidin. In addition, we cloned the corresponding rat and human orthologue cDNAs. Both mouse and human genes named HEPC are constituted of 3 exons and 2 introns and are located on chromosome 7 and 19, respectively, in close proximity to USF2 gene. In mouse and human, HEPC mRNA was predominantly expressed in the liver. During both in vivo and in vitro studies, HEPC mRNA expression was enhanced in mouse hepatocytes under the effect of lipopolysaccharide. Finally, to analyze the intracellular localization of the predicted protein, we used the green fluorescent protein chimera expression vectors. The murine green fluorescent protein-prohepcidin protein was exclusively localized in the nucleus. When the putative nuclear localization signal was deleted, the resulting protein was addressed to the cytoplasm. Taken together, our data strongly suggest that the product of the new liver-specific gene HEPC might play a specific role during iron overload and exhibit additional functions distinct from its antimicrobial activity.

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Section: Discussioncontrasting

confidence: 56%

A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload

Pigeon

Ilyin

Courselaud

et al. 2001

Journal of Biological Chemistry

1,506

1,264

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“…The fat body is the primary organ responsible for this humoral defense in the fly and secretes a battery of antimicrobial peptides in response to infection (reviewed in Ref. 6). …”

mentioning

confidence: 99%

The Lipopolysaccharide-activated Toll-like Receptor (TLR)-4 Induces Synthesis of the Closely Related Receptor TLR-2 in Adipocytes

Lin¹,

Lee²,

Berg³

et al. 2000

Journal of Biological Chemistry

318

230

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The central regulatory role of the adipocyte in whole body energy homeostasis is well established. However, recent findings suggest that preadipocytes and adipocytes may play an important physiological role in the regulation of both the innate and adaptive immune response. To systematically characterize the molecular machinery of the adipocyte that mediates the recognition of pathogens, we have focused our analysis on the recently identified Toll-like receptors (TLRs). These receptors have been implicated as mediators of the cellular response to bacterial lipopolysacharides (LPSs). Here, we report the cloning and functional characterization of mouse TLR-2 from 3T3-L1 adipocytes. TLR-2 synthesis is strongly induced in the adipocyte by LPS, TNF␣, and the yeast cell wall extract zymosan. TLR-2 undergoes a lengthy intracellular maturation process with a half-life of exit from the ER of approximately 3 h. Furthermore, LPS treatment of adipocytes results in dramatic changes at the level of gene expression, including the synthesis of a distinct set of secretory proteins such as interleukin-6. Our studies demonstrate the presence of a fully intact pathway of innate immunity in the adipocyte that can be activated by LPS binding to the cell surface and results in the secretion of immunomodulatory molecules.

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“…[1][2][3][4]. The insect immune response has cellular and humoral components hallmarked, respectively, by the mobilization of hemocytes and production of antimicrobial proteins.…”

mentioning

confidence: 99%

Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity

Bernal

Kimbrell

2000

Proc. Natl. Acad. Sci. U.S.A.

139

123

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Thor has been identified as a new type of gene involved in Drosophila host immune defense. Thor is a member of the 4E-binding protein (4E-BP) family, which in mammals has been defined as critical regulators in a pathway that controls initiation of translation through binding eukaryotic initiation factor 4E (eIF4E). Without an infection, Thor is expressed during all developmental stages and transcripts localize to a wide variety of tissues, including the reproductive system. In response to bacterial infection and, to a lesser extent, by wounding, Thor is up-regulated. The Thor promoter has the canonical NF B and associated GATA recognition sequences that have been shown to be essential for immune induction, as well as other sequences commonly found for Drosophila immune response genes, including interferon-related regulatory sequences. In survival tests, Thor mutants show symptoms of being immune compromised, indicating that Thor may be critical in host defense. In contrast to Thor, Drosophila eIF4E is not induced by bacterial infection. These findings for Thor provide the first evidence that a 4E-BP family member has a role in immune induction in any organism. Further, no gene in the translation initiation pathway that includes 4E-BP has been previously found to be immune induced. Our results suggest either a role for translational regulation in humoral immunity or a new, nontranslational function for 4E-BP type genes.

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Antimicrobial peptide defense in Drosophila

Cited by 164 publications

References 85 publications

A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload

A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload

The Lipopolysaccharide-activated Toll-like Receptor (TLR)-4 Induces Synthesis of the Closely Related Receptor TLR-2 in Adipocytes

Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity

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