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Relish, a central factor in the control of humoral but not cellular immunity in Drosophila
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Umeå Center for Molecular Pathogenesis, Umeå university.
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1999 (English)In: Molecular cell, ISSN 1097-2765, Vol. 4, no 5, 827-37 p.Article in journal (Refereed) Published
Abstract [en]

The NF-κB-like Relish gene is complex, with four transcripts that are all located within an intron of the Nmdmc gene. Using deletion mutants, we show that Relish is specifically required for the induction of the humoral immune response, including both antibacterial and antifungal peptides. As a result, the Relish mutants are very sensitive to infection. A single cell of E. cloacae is sufficient to kill a mutant fly, and the mutants show increased susceptibility to fungal infection. In contrast, the blood cell population, the hematopoietic organs, and the phagocytic, encapsulation, and melanization responses are normal. Our results illustrate the importance of the humoral response in Drosophila immunity and demonstrate that Relish plays a key role in this response.

Place, publisher, year, edition, pages
Elsevier , 1999. Vol. 4, no 5, 827-37 p.
National Category
Cell Biology
Research subject
Cellbiology
Identifiers
URN: urn:nbn:se:su:diva-23156DOI: 10.1016/S1097-2765(00)80392-5OAI: oai:DiVA.org:su-23156DiVA: diva2:190441
Note
Part of urn:nbn:se:su:diva-170Available from: 2004-05-13 Created: 2004-05-13 Last updated: 2009-12-22Bibliographically approved
In thesis
1. Relish and the Regulation of Antimicrobial Peptides in Drosophila melanogaster
Open this publication in new window or tab >>Relish and the Regulation of Antimicrobial Peptides in Drosophila melanogaster
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The fruit fly Drosophila melanogaster has been a powerful model system in which to study the immune response. When microorganisms breach the mechanical barrier of the insect, phagocytosing cells and a battery of induced antimicrobial molecules rapidly attack them. These antimicrobial peptides can reach micromolar concentrations within a few hours. This immediate response is reminiscent of the mammalian innate immune response and utilizes transcription factors of the NF-κB family.

We have generated loss-of-function mutants of the NF-κB-like transcription factor Relish in order to investigate Relish's role in the Drosophila immune response to microbes. Relish mutant flies have a severely impaired immune response to Gram-negative (G-) bacteria and some Gram-positive (G+) bacteria and fungi and succumb to an otherwise harmless infection. The main reason for the high susceptibility to infection is that these mutant flies fail to induce the antimicrobial peptide genes. The cellular responses appear to be normal.

Relish is retained in the cytoplasm in an inactive state. We designed a set of expression plasmids to investigate the requirements for activation of Relish in a hemocyte cell line after stimulation with bacterial lipopolysaccharide. Signal-induced phosphorylation of Relish followed by endoproteolytic processing at the caspase-like target motif in the linker region released the inhibitory ankyrin-repeat (ANK) domain from the DNA binding Rel homology domain (RHD). Separation from the ANK domain allowed the RHD to move into the nucleus and initiate transcription of target genes like those that encode the inducible antimicrobial peptides, likely by binding to κB-like sites in the promoter region.

By studying the immune response of the Relish mutant flies in combination with mutants for another NF-κB-like protein, Dorsal-related immunity factor (Dif), we found that the Drosophila immune system can distinguish between various microbes and generate a differential response by activating the Toll/Dif and Imd/Relish pathways. The recognition of foreign microorganisms is believed to occur through pattern recognition receptors (PRRs) that have affinity for selective pathogen-associated molecular patterns (PAMPs). We found that the Drosophila PRRs can recognize G- bacteria as a group. Interestingly, the PRRs are specific enough to distinguish between peptidoglycans from G+ bacteria such as Micrococcus luteus and Bacillus megaterium and fungal PAMPs from Beauveria bassiana and Geotrichum candidum.

This thesis also investigates the expression of the antimicrobial peptide genes, Diptericin B and Attacin C, and the putative intracellular antimicrobial peptide gene Attacin D, and explores a potential evolutionary link between them.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2004. 49 p.
Keyword
Drosophila immunity, NF-kappaB, Relish, antimicrobial peptides
National Category
Developmental Biology
Identifiers
urn:nbn:se:su:diva-170 (URN)91-7265-897-5 (ISBN)
Public defence
2004-06-02, hörsalen, Frescati backe, Svante Arrhenius väg 21 A, Stockholm, 13:00
Opponent
Supervisors
Available from: 2004-05-13 Created: 2004-05-13 Last updated: 2011-03-28Bibliographically approved

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