Mānuka honey-derived methylglyoxal enhances microbial sensing by mucosal-associated invariant T cells. Issue 7 (3rd July 2020)

• Record Type: Journal Article
• Authors: Tang, Jeffry S.; Compton, Benjamin J.; Marshall, Andrew; Anderson, Regan; Li, Yanyan; van der Woude, Hannah; Hermans, Ian F.; Painter, Gavin F.; Gasser, Olivier
• Is Part Of: Food & function. Volume 11:Issue 7(2020)
• Page Start: 5782
• Page End: 5787
• Publication Date: 2020-07-03
• Subjects: Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; Nutrition -- Periodicals; 664.07
• DOI: 10.1039/d0fo01153c
• Languages: English
• ISSNs: 2042-6496

Abstract

Abstract : Mānuka honey-derived methylglyoxal enhanced MAIT cell activation by increasing conversion of microbial 5-A-RU to the potent MAIT cell activator, 5-OP-RU. 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.