Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion
Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune re...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02942/full |
| _version_ | 1818030415202484224 |
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| author | Mana Miyakoda Mana Miyakoda Ganchimeg Bayarsaikhan Daisuke Kimura Daisuke Kimura Masoud Akbari Heiichiro Udono Katsuyuki Yui Katsuyuki Yui |
| author_facet | Mana Miyakoda Mana Miyakoda Ganchimeg Bayarsaikhan Daisuke Kimura Daisuke Kimura Masoud Akbari Heiichiro Udono Katsuyuki Yui Katsuyuki Yui |
| author_sort | Mana Miyakoda |
| collection | DOAJ |
| description | Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells. |
| first_indexed | 2024-12-10T05:35:13Z |
| format | Article |
| id | doaj.art-cca91bedc9f0464bb15b753cb292898b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T05:35:13Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-cca91bedc9f0464bb15b753cb292898b2022-12-22T02:00:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.02942422158Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell ExpansionMana Miyakoda0Mana Miyakoda1Ganchimeg Bayarsaikhan2Daisuke Kimura3Daisuke Kimura4Masoud Akbari5Heiichiro Udono6Katsuyuki Yui7Katsuyuki Yui8Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, JapanResearch and Education Center for Drug Fostering and Evolution, School of Pharmaceutical Sciences, Nagasaki University, Nagasaki, JapanDivision of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, JapanDivision of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, JapanDepartment of Health, Sports, and Nutrition, Faculty of Health and Welfare, Kobe Women's University, Kobe, JapanDivision of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, JapanDepartment of Immunology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, JapanDivision of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, JapanGraduate School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, JapanAdaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells.https://www.frontiersin.org/article/10.3389/fimmu.2018.02942/fullmalariaγδ T cellclonal expansionprotectionmetforminmetabolism |
| spellingShingle | Mana Miyakoda Mana Miyakoda Ganchimeg Bayarsaikhan Daisuke Kimura Daisuke Kimura Masoud Akbari Heiichiro Udono Katsuyuki Yui Katsuyuki Yui Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion Frontiers in Immunology malaria γδ T cell clonal expansion protection metformin metabolism |
| title | Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion |
| title_full | Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion |
| title_fullStr | Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion |
| title_full_unstemmed | Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion |
| title_short | Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion |
| title_sort | metformin promotes the protection of mice infected with plasmodium yoelii independently of γδ t cell expansion |
| topic | malaria γδ T cell clonal expansion protection metformin metabolism |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02942/full |
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