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Issue 7, 2020
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Mānuka honey-derived methylglyoxal enhances microbial sensing by mucosal-associated invariant T cells

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Abstract

Methylglyoxal (MGO) is the main antimicrobial determinant associated with using Mānuka Honey as a topical dressing. While direct mechanisms of Mānuka honey MGO's antimicrobial activity have been demonstrated, such as disruption of bacterial fimbria and flagella, no interaction of Mānuka honey-derived MGO with antimicrobial effector cells of the immune system, such as mucosal-associated invariant T cells (MAIT cells), has yet been reported. MAIT cells are an abundant subset of human T cells, critical for regulating a diverse range of immune functions, including antimicrobial defense mechanisms but also mucosal barrier integrity. MAIT cells become activated by recognition of an important microbial metabolite, 5-amino-6-D-ribitylaminouracil (5-A-RU), which is produced by a wide range of microbial pathogens and commensals. Recognition is afforded when 5-A-RU condenses with mammalian-cell derived MGO to form the potent MAIT cell activator, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU). Formation of 5-OP-RU and its subsequent presentation to MAIT cells by major histocompatibility (MHC)-related molecule 1 (MR1) facilitates host–pathogen and host–commensal interactions. While MGO is a metabolite naturally present in mammalian cells, it is unclear whether exogenous dietary MGO sources, such as those obtained from Mānuka honey intake, can contribute to 5-OP-RU formation and enhance MAIT cell activation. In this work, we report that endogenous MGO is the rate-limiting substrate for converting microbial 5-A-RU to 5-OP-RU and that Mānuka honey-derived MGO significantly enhances MAIT cell activation in vitro. Our findings posit a novel mechanism by which intake of a food item, such as Mānuka honey, can potentially support immune homeostasis by enhancing MAIT cell-specific microbial sensing.

Graphical abstract: Mānuka honey-derived methylglyoxal enhances microbial sensing by mucosal-associated invariant T cells

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Supplementary files

Article information


Submitted
05 May 2020
Accepted
19 Jun 2020
First published
03 Jul 2020

This article is Open Access

Food Funct., 2020,11, 5782-5787
Article type
Communication

Mānuka honey-derived methylglyoxal enhances microbial sensing by mucosal-associated invariant T cells

J. S. Tang, B. J. Compton, A. Marshall, R. Anderson, Y. Li, H. van der Woude, I. F. Hermans, G. F. Painter and O. Gasser, Food Funct., 2020, 11, 5782
DOI: 10.1039/D0FO01153C

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