Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants
The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and Imd-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that cer...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2019-06-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/12/6/dmm037721 |
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| author | Mayo Araki Massanori Kurihara Suzuko Kinoshita Rie Awane Tetsuya Sato Yasuyuki Ohkawa Yoshihiro H. Inoue |
| author_facet | Mayo Araki Massanori Kurihara Suzuko Kinoshita Rie Awane Tetsuya Sato Yasuyuki Ohkawa Yoshihiro H. Inoue |
| author_sort | Mayo Araki |
| collection | DOAJ |
| description | The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and Imd-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells; however, little is known about their anti-tumour effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-seq analysis, we found many immunoresponsive genes, including those encoding AMPs, to be upregulated in these mutants. Downregulation of these pathways by either a Toll or imd mutation enhanced the tumour phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress the progression of haematopoietic tumours by inducing AMP gene expression. Overexpression of any one of the five AMPs studied resulted in enhanced apoptosis in mutant LGs, whereas no apoptotic signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating haemocyte-like cells, which were associated with the LG regions and showed reduced cell-to-cell adhesion in the mutants. By contrast, the AMP Diptericin was directly localised at the tumour site without intermediating haemocytes. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells. |
| first_indexed | 2024-12-11T05:14:45Z |
| format | Article |
| id | doaj.art-f70e16a55e6d4746a3c1db5230f037fa |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-11T05:14:45Z |
| publishDate | 2019-06-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-f70e16a55e6d4746a3c1db5230f037fa2022-12-22T01:19:51ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112019-06-0112610.1242/dmm.037721037721Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutantsMayo Araki0Massanori Kurihara1Suzuko Kinoshita2Rie Awane3Tetsuya Sato4Yasuyuki Ohkawa5Yoshihiro H. Inoue6 Department of Insect Biomedical Research, Centre for Advanced Insect Research Promotion, Kyoto Institute of Technology, Kyoto 606-0962, Japan Department of Insect Biomedical Research, Centre for Advanced Insect Research Promotion, Kyoto Institute of Technology, Kyoto 606-0962, Japan Department of Insect Biomedical Research, Centre for Advanced Insect Research Promotion, Kyoto Institute of Technology, Kyoto 606-0962, Japan Department of Insect Biomedical Research, Centre for Advanced Insect Research Promotion, Kyoto Institute of Technology, Kyoto 606-0962, Japan Medical Institute of Bioregulation, Kyushu University, Kyushu 812-0054, Japan Medical Institute of Bioregulation, Kyushu University, Kyushu 812-0054, Japan Department of Insect Biomedical Research, Centre for Advanced Insect Research Promotion, Kyoto Institute of Technology, Kyoto 606-0962, Japan The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and Imd-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells; however, little is known about their anti-tumour effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-seq analysis, we found many immunoresponsive genes, including those encoding AMPs, to be upregulated in these mutants. Downregulation of these pathways by either a Toll or imd mutation enhanced the tumour phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress the progression of haematopoietic tumours by inducing AMP gene expression. Overexpression of any one of the five AMPs studied resulted in enhanced apoptosis in mutant LGs, whereas no apoptotic signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating haemocyte-like cells, which were associated with the LG regions and showed reduced cell-to-cell adhesion in the mutants. By contrast, the AMP Diptericin was directly localised at the tumour site without intermediating haemocytes. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells.http://dmm.biologists.org/content/12/6/dmm037721DrosophilaInnate immunityAMPsLymph glandFat bodyCytotoxicity |
| spellingShingle | Mayo Araki Massanori Kurihara Suzuko Kinoshita Rie Awane Tetsuya Sato Yasuyuki Ohkawa Yoshihiro H. Inoue Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants Disease Models & Mechanisms Drosophila Innate immunity AMPs Lymph gland Fat body Cytotoxicity |
| title | Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants |
| title_full | Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants |
| title_fullStr | Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants |
| title_full_unstemmed | Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants |
| title_short | Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants |
| title_sort | anti tumour effects of antimicrobial peptides components of the innate immune system against haematopoietic tumours in drosophila mxc mutants |
| topic | Drosophila Innate immunity AMPs Lymph gland Fat body Cytotoxicity |
| url | http://dmm.biologists.org/content/12/6/dmm037721 |
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