Presentation_1_Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion.pdf Mana Miyakoda Ganchimeg Bayarsaikhan Daisuke Kimura Masoud Akbari Heiichiro Udono Katsuyuki Yui 10.3389/fimmu.2018.02942.s001 https://frontiersin.figshare.com/articles/presentation/Presentation_1_Metformin_Promotes_the_Protection_of_Mice_Infected_With_Plasmodium_yoelii_Independently_of_T_Cell_Expansion_pdf/7459574 <p>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<sup>+</sup> and Vγ2<sup>+</sup> 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.</p> 2018-12-13 04:16:18 malaria γδ T cell clonal expansion protection metformin metabolism