Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes

Abstract Diabetes mellitus (DM) patients are at an increased risk of complications following influenza-virus infection, seasonal vaccination (SV) is recommended. However, SV with trivalent influenza vaccine (TIV) can induce antibody and type-I interferon (IFN) responses, and the effect of anti-DM tr...

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Autores principales:	Wipawee Saenwongsa, Arnone Nithichanon, Malinee Chittaganpitch, Kampaew Buayai, Chidchamai Kewcharoenwong, Boonyarat Thumrongwilainet, Patcharavadee Butta, Tanapat Palaga, Yoshimasa Takahashi, Manabu Ato, Ganjana Lertmemongkolchai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29f147898f844010845b81693da79602
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spelling	oai:doaj.org-article:29f147898f844010845b81693da796022021-12-02T16:23:10ZMetformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes10.1038/s41598-020-60213-02045-2322https://doaj.org/article/29f147898f844010845b81693da796022020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-60213-0https://doaj.org/toc/2045-2322Abstract Diabetes mellitus (DM) patients are at an increased risk of complications following influenza-virus infection, seasonal vaccination (SV) is recommended. However, SV with trivalent influenza vaccine (TIV) can induce antibody and type-I interferon (IFN) responses, and the effect of anti-DM treatment on these responses is incompletely understood. We evaluated the antibody response and IFN-α expression in individuals with and without type 2 DM (T2DM) following SV, and examined the effects on anti-DM treatment. TIV elicited sero-protection in all groups, but antibody persistency was <8 months, except for the antibody response to B-antigens in non-DM. T2DM impaired the IgG avidity index, and T2DM showed a significantly decreased response against H1N1 and H3N2, in addition to delaying and reducing haemagglutination-inhibition persistency against influenza B-antigens in DM groups treated with metformin (Met-DM) or glibenclamide (GB-DM). Following TIV, the Met-DM and GB-DM groups exhibited reduced IFN-α expression upon stimulation with whole- and split-virion influenza vaccines. Suppression of IFN-α expression in the Met-DM group was associated with a reduction in the mechanistic target of rapamycin complex-1 pathway and impaired IgG avidity index. Thus, single-dose TIV each year might not be suitable for T2DM. Our data could aid the development of an efficacious influenza vaccine for T2DM.Wipawee SaenwongsaArnone NithichanonMalinee ChittaganpitchKampaew BuayaiChidchamai KewcharoenwongBoonyarat ThumrongwilainetPatcharavadee ButtaTanapat PalagaYoshimasa TakahashiManabu AtoGanjana LertmemongkolchaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wipawee Saenwongsa Arnone Nithichanon Malinee Chittaganpitch Kampaew Buayai Chidchamai Kewcharoenwong Boonyarat Thumrongwilainet Patcharavadee Butta Tanapat Palaga Yoshimasa Takahashi Manabu Ato Ganjana Lertmemongkolchai Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes
description	Abstract Diabetes mellitus (DM) patients are at an increased risk of complications following influenza-virus infection, seasonal vaccination (SV) is recommended. However, SV with trivalent influenza vaccine (TIV) can induce antibody and type-I interferon (IFN) responses, and the effect of anti-DM treatment on these responses is incompletely understood. We evaluated the antibody response and IFN-α expression in individuals with and without type 2 DM (T2DM) following SV, and examined the effects on anti-DM treatment. TIV elicited sero-protection in all groups, but antibody persistency was <8 months, except for the antibody response to B-antigens in non-DM. T2DM impaired the IgG avidity index, and T2DM showed a significantly decreased response against H1N1 and H3N2, in addition to delaying and reducing haemagglutination-inhibition persistency against influenza B-antigens in DM groups treated with metformin (Met-DM) or glibenclamide (GB-DM). Following TIV, the Met-DM and GB-DM groups exhibited reduced IFN-α expression upon stimulation with whole- and split-virion influenza vaccines. Suppression of IFN-α expression in the Met-DM group was associated with a reduction in the mechanistic target of rapamycin complex-1 pathway and impaired IgG avidity index. Thus, single-dose TIV each year might not be suitable for T2DM. Our data could aid the development of an efficacious influenza vaccine for T2DM.
format	article
author	Wipawee Saenwongsa Arnone Nithichanon Malinee Chittaganpitch Kampaew Buayai Chidchamai Kewcharoenwong Boonyarat Thumrongwilainet Patcharavadee Butta Tanapat Palaga Yoshimasa Takahashi Manabu Ato Ganjana Lertmemongkolchai
author_facet	Wipawee Saenwongsa Arnone Nithichanon Malinee Chittaganpitch Kampaew Buayai Chidchamai Kewcharoenwong Boonyarat Thumrongwilainet Patcharavadee Butta Tanapat Palaga Yoshimasa Takahashi Manabu Ato Ganjana Lertmemongkolchai
author_sort	Wipawee Saenwongsa
title	Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes
title_short	Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes
title_full	Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes
title_fullStr	Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes
title_full_unstemmed	Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes
title_sort	metformin-induced suppression of ifn-α via mtorc1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/29f147898f844010845b81693da79602
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Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes

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