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The Immune Phenotype of Three Drosophila Leukemia Models
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. Institute of Experimental Biology, 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.
Number of Authors: 4
2017 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 7, no 7, 2139-2149 p.Article in journal (Refereed) Published
Abstract [en]

Many leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading to general weakening (cachexia). Both adaptive and innate immunity are affected. The fruit fly Drosophila melanogaster has an innate immune system, including cells of the myeloid lineage (hemocytes). To study Drosophila immunity and physiology during leukemia, we established three models by driving expression of a dominant-active version of the Ras oncogene (Ras(V12)) alone or combined with knockdowns of tumor suppressors in Drosophila hemocytes. Our results show that phagocytosis, hemocyte migration to wound sites, wound sealing, and survival upon bacterial infection of leukemic lines are similar to wild type. We find that in all leukemic models the two major immune pathways (Toll and Imd) are dysregulated. Toll-dependent signaling is activated to comparable extents as after wounding wild-type larvae, leading to a proinflammatory status. In contrast, Imd signaling is suppressed. Finally, we notice that adult tissue formation is blocked and degradation of cell masses during metamorphosis of leukemic lines, which is akin to the state of cancer-dependent cachexia. To further analyze the immune competence of leukemic lines, we used a natural infection model that involves insect-pathogenic nematodes. We identified two leukemic lines that were sensitive to nematode infections. Further characterization demonstrates that despite the absence of behavioral abnormalities at the larval stage, leukemic larvae show reduced locomotion in the presence of nematodes. Taken together, this work establishes new Drosophila models to study the physiological, immunological, and behavioral consequences of various forms of leukemia.

Place, publisher, year, edition, pages
2017. Vol. 7, no 7, 2139-2149 p.
Keyword [en]
Ras, oncogene, nematodes, insect immunity, hemocyte, Genetics of Immunity
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-145330DOI: 10.1534/g3.117.039487ISI: 000404991600012OAI: oai:DiVA.org:su-145330DiVA: diva2:1128800
Available from: 2017-07-28 Created: 2017-07-28 Last updated: 2017-07-28Bibliographically approved

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Arefin, BadrulKrautz, RobertTheopold, Ulrich
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