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Immuno-antibiotics: Targeting microbial metabolic pathways sensed by unconventional T cells

Eberl, Matthias, Oldfield, Eric and Herrmann, Thomas 2021. Immuno-antibiotics: Targeting microbial metabolic pathways sensed by unconventional T cells. Immunotherapy Advances 10.1093/immadv/ltab005

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Human Vγ9/Vδ2 T cells, mucosal-associated invariant T (MAIT) cells and other unconventional T cells are specialised in detecting microbial metabolic pathway intermediates that are absent in humans. The recognition by such semi-invariant innate-like T cells of compounds like (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), the penultimate metabolite in the MEP isoprenoid biosynthesis pathway, and intermediates of the riboflavin biosynthesis pathway and their metabolites allows the immune system to rapidly sense pathogen-associated molecular patterns that are shared by a wide range of micro-organisms. Given the essential nature of these metabolic pathways for microbial viability, they have emerged as promising targets for the development of novel antibiotics. Here, we review recent findings that link enzymatic inhibition of microbial metabolism with alterations in the levels of unconventional T cell ligands produced by treated micro-organisms that have given rise to the concept of ‘immuno-antibiotics’: combining direct antimicrobial activity with an immunotherapeutic effect via modulation of unconventional T cell responses.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
Systems Immunity Research Institute (SIURI)
ISSN: 2732-4303
Date of First Compliant Deposit: 7 April 2021
Date of Acceptance: 22 March 2021
Last Modified: 07 Apr 2021 13:20

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