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The Drosophila Chitinase-Like Protein IDGF3 Is Involved in Protection against Nematodes and in Wound Healing
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of South Bohemia, Czech Republic.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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Number of Authors: 8
2016 (English)In: Journal of Innate Immunity, ISSN 1662-811X, E-ISSN 1662-8128, Vol. 8, no 2, 199-210 p.Article in journal (Refereed) Published
Abstract [en]

Chitinase-like proteins (CLPs) of the 18 glycosyl hydrolase family retain structural similarity to chitinases but lack enzymatic activity. Although CLPs are upregulated in several human disorders that affect regenerative and inflammatory processes, very little is known about their normal physiological function. We show that an insect CLP (Drosophila imaginal disc growth factor 3, IDGF3) plays an immune-protective role during entomopathogenic nematode (EPN) infections. During these infections, nematodes force their entry into the host via border tissues, thus creating wounds. Whole-genome transcriptional analysis of nematode-infected wildtype and Idgf3 mutant larvae have shown that, in addition to the regulation of genes related to immunity and wound closure, IDGF3 represses Jak/STAT and Wingless signaling. Further experiments have confirmed that IDGF3 has multiple roles in innate immunity. It serves as an essential component required for the formation of hemolymph clots that seal wounds, and Idgf3 mutants display an extended developmental delay during wound healing. Altogether, our findings indicate that vertebrate and invertebrate CLP proteins function in analogous settings and have a broad impact on inflammatory reactions and infections. This opens the way to further genetic analysis of Drosophila IDGF3 and will help to elucidate the exact molecular context of CLP function.

Place, publisher, year, edition, pages
2016. Vol. 8, no 2, 199-210 p.
Keyword [en]
Chitinase-like proteins, Imaginal disc growth factor, Hemolymph clot, Wound healing, Nematode infection, Insect immunity
National Category
Biological Sciences
Research subject
Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-129978DOI: 10.1159/000442351ISI: 000372510800009PubMedID: 26694862OAI: oai:DiVA.org:su-129978DiVA: diva2:926559
Available from: 2016-05-09 Created: 2016-05-09 Last updated: 2016-10-05Bibliographically approved
In thesis
1. Molecular characterization of the Drosophila responses towards nematodes
Open this publication in new window or tab >>Molecular characterization of the Drosophila responses towards nematodes
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A sophisticated evolutionary conserved innate immune system has evolved in insects to fight pathogens and to restrict damage in harmful (danger) situations including cancer. A significant amount of knowledge about different infection models in Drosophila has been generated in past decades, which revealed functional resemblances and implications for vertebrate systems. However, how Drosophila responds towards multicellular parasitic nematodes and in danger situations is still little understood. Therefore, the aim of the thesis was to characterize multiple aspects of the host defense in the two important contexts mentioned above.

We analyzed the transcriptome profiles of nematode-infected Drosophila larvae with uninfected samples. For this we employed the entomopathogenic nematode Heterorhabditis bacteriophora with its symbiont Photorhabdus luminescence to infect Drosophila larvae. We found 642 genes were differentially regulated upon infection. Among them a significant portion belonged to immune categories. Further functional analysis identified a thioester containing protein TEP3, a recognition protein GNBP-like 3, the basement membrane component protein Glutactin and several other small peptides. Upon loss or reduced expression of these genes hosts showed mortality during nematode infections. This study uncovers a novel function for several of the genes in immunity.

Furthermore, we investigated the cellular response towards nematodes. When we eliminated hemocytes genetically (referred to as hml-apo) in Drosophila, we found hml-apo larvae are resistant to nematodes. Subsequent characterization of hml-apo larvae showed massive lamellocyte differentiation (another blood cell type which is rare in naïve larvae), emergence of melanotic masses, up- and down-regulation of Toll and Imd signaling respectively suggesting a pro-inflammatory response. Moreover, a striking defective leg phenotype in adult escapers from pupal lethality was observed. We identified nitric oxide (NO) as a key regulator of these processes. We also showed that imaginal disc growth factors 3 (IDGF3): (a) protects hosts against nematodes, (b) is a clotting component and (c) negatively regulates Wnt and JAK/STAT signaling. To follow larval behavior in the presence or absence of nematodes we monitored Drosophila larval locomotion behaviors using FIMtrack (a recently devised automated method) to elucidate evasive strategies of hosts. Finally, we characterized host defenses in three Drosophila leukemia models with and without nematode infection. Taken together, these studies shed light on host responses in two crucial circumstances, nematode infections and danger situations.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2016. 65 p.
Keyword
Drosophila, nematodes, infection, danger situations, immune response, coagulation, apoptosis, nitric oxide, leukemia
National Category
Biochemistry and Molecular Biology Genetics Immunology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:su:diva-134346 (URN)978-91-7649-535-3 (ISBN)978-91-7649-536-0 (ISBN)
Public defence
2016-11-24, Vivi Täckholmsalen (Q-salen), NPQ-huset, Svante Arrhenius väg 20, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 3: Manuscript.

Available from: 2016-11-01 Created: 2016-10-05 Last updated: 2017-05-04Bibliographically approved

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