Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 552052
Title Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects
Author(s) Lachmandas, Ekta; Eckold, Clare; Böhme, Julia; Koeken, Valerie A.C.M.; Marzuki, Mardiana Binte; Blok, Bastiaan; Arts, Rob J.W.; Chen, Jinmiao; Teng, Karen W.W.; Ratter, Jacqueline; Smolders, Elise J.; Heuvel, Corina Van den; Stienstra, Rinke; Dockrell, Hazel M.; Newell, Evan; Netea, Mihai G.; Singhal, Amit; Cliff, Jacqueline M.; Crevel, Reinout Van
Source The Journal of Infectious Diseases 220 (2019)1. - ISSN 0022-1899 - p. 139 - 150.
DOI https://doi.org/10.1093/infdis/jiz064
Department(s) Human Nutrition & Health
Nutrition, Metabolism and Genomics
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2019
Keyword(s) antimycobacterial mechanisms - gene transcription - host-directed therapy - Metformin - tuberculosis
Abstract

BACKGROUND: Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis. METHODS: We investigated in vitro and in vivo effects of metformin in humans. RESULTS: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production. CONCLUSION: Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis.

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