MAIT cells and the microbiome

Abstract

Mucosal associated invariant T (MAIT) cells are innate-like T lymphocytes, strikingly enriched at mucosal surfaces and characterized by a semi-invariant αβ T cell receptor (TCR) recognizing microbial derived intermediates of riboflavin synthesis presented by the MHC-Ib molecule MR1. At barrier sites MAIT cells occupy a prime position for interaction with commensal microorganisms, comprising the microbiota. The microbiota is a rich source of riboflavin derived antigens required in early life to promote intra-thymic MAIT cell development and sustain a life-long population of tissue resident cells. A symbiotic relationship is thought to be maintained in health whereby microbes promote maturation and homeostasis, and in turn MAIT cells can engage a TCR-dependent “tissue repair” program in the presence of commensal organisms conducive to sustaining barrier function and integrity of the microbial community. MAIT cell activation can be induced in a MR1-TCR dependent manner or through MR1-TCR independent mechanisms via pro-inflammatory cytokines interleukin (IL)-12/-15/-18 and type I interferon. MAIT cells provide immunity against bacterial, fungal and viral pathogens. However, MAIT cells may have deleterious effects through insufficient or exacerbated effector activity and have been implicated in autoimmune, inflammatory and allergic conditions in which microbial dysbiosis is a shared feature. In this review we summarize the current knowledge on the role of the microbiota in the development and maintenance of circulating and tissue resident MAIT cells. We also explore how microbial dysbiosis, alongside changes in intestinal permeability and imbalance between pro- and anti-inflammatory components of the immune response are together involved in the potential pathogenicity of MAIT cells. Whilst there have been significant improvements in our understanding of how the microbiota shapes MAIT cell function, human data are relatively lacking, and it remains unknown if MAIT cells can conversely influence the composition of the microbiota. We speculate whether, in a human population, differences in microbiomes might account for the heterogeneity observed in MAIT cell frequency across mucosal sites or between individuals, and response to therapies targeting T cells. Moreover, we speculate whether manipulation of the microbiota, or harnessing MAIT cell ligands within the gut or disease-specific sites could offer novel therapeutic strategies.

Mucosal-associated invariant T cells in cancer: dual roles, complex interactions and therapeutic potential

“…Moreover, the TME itself can alter the local microbiota, creating a feedback loop that further influences MAIT cell function ( 14 , 126 , 127 ). Tumor-induced changes in the local environment, such as hypoxia or altered nutrient availability, can select for microbial populations that either exacerbate or mitigate tumor progression ( 127 ).…”

“…This unique antigen recognition mechanism allows MAIT cells to respond to a wide range of microbial infections, as these metabolite antigens are conserved across many bacterial and fungal species, not found in human cells ( 1 , 6 , 8 – 12 ). MAIT cells are also involved in tissue repair and regeneration, privileged interaction between defined members of the microbiota, which sequentially controls both tissue-imprinting and subsequent responses to injury ( 13 , 14 ).…”

Role of innate T cells in necrotizing enterocolitis

“…Many of the non-peptide antigens that activate innate T cells are microbially derived ( 24 – 31 ). Therefore, their development and function are changed by the microbiome ( 32 – 34 ).…”

A comprehensive perspective on the interaction between gut microbiota and COVID-19 vaccines

“…Commensal bacteria that produce vitamin B ligands can directly stimulate MAIT cells and induce their proliferation and cytokine production. Therefore, depleted commensal symbionts, such as Roseburia and Eubacterium , may impair the activation and function of MAIT cells by reducing their stimulation, potentially resulting in decreased MAIT cell responses to SARS-CoV-2 infections, as well as reduced MAIT cell-mediated regulation of other immune cells 58 . The efficacy of a vaccine depends on the generation of robust and long-lasting immune responses against the target antigen.…”