Augmentation of the Riboflavin-Biosynthetic Pathway Enhances Mucosa-Associated Invariant T (MAIT) Cell Activation and Diminishes Mycobacterium tuberculosis Virulence

Dey, Ruchi Jain; Dey, Bappaditya; Harriff, Melanie J.; Canfield, Elizabeth T.; Lewinsohn, David; Bishai, William R.

doi:10.1128/mbio.03865-21

Cited by 20 publications

(12 citation statements)

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“…Indeed, multidrug-resistant S. typhimurium reduces MAIT cell activation property by altered gene expressions in the riboflavin synthetic pathway ( Preciado-Llanes et al, 2020 ). Augmentation of riboflavin synthetic pathway in Mycobacterium tuberculosis enhances MAIT cell-dependent protective responses ( Dey et al, 2022 ). Intriguingly, some clinical isolates of multidrug resistant M. tuberculosis and Mycobacterium.…”

Section: Discussionmentioning

confidence: 99%

The intracellular pathogen Francisella tularensis escapes from adaptive immunity by metabolic adaptation

et al. 2022

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Intracellular pathogens lose many metabolic genes during their evolution from free-living bacteria, but the pathogenic consequences of their altered metabolic programs on host immunity are poorly understood. Here, we show that a pathogenic strain of Francisella tularensis subsp. tularensis (FT) has five amino acid substitutions in RibD, a converting enzyme of the riboflavin synthetic pathway responsible for generating metabolites recognized by mucosal-associated invariant T (MAIT) cells. Metabolites from a free-living strain, F. tularensis subsp. novicida (FN), activated MAIT cells in a T-cell receptor (TCR)–dependent manner, whereas introduction of FT-type ribD to the free-living strain was sufficient to attenuate this activation in both human and mouse MAIT cells. Intranasal infection in mice showed that the ribDFT-expressing FN strain induced impaired Th1-type MAIT cell expansion and resulted in reduced bacterial clearance and worsened survival compared with the wild-type free-living strain FN. These results demonstrate that F. tularensis can acquire immune evasion capacity by alteration of metabolic programs during evolution.

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Section: Discussionmentioning

confidence: 99%

The intracellular pathogen Francisella tularensis escapes from adaptive immunity by metabolic adaptation

et al. 2022

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“…Transgenic mice overexpressing TCR specific for MAIT cells can overcome this inherent problem but still suffer from aberrant MAIT cell function, and/or the absence of other T cells (Godfrey et al, 2019). In this respect, it is interesting to note that CAST/EiJ, a strain expressing more MAIT cells than other laboratory strains, exhibited diminished Mycobacteria tuberculosis virulence (Dey et al, 2022). Furthermore, Cast/B6 mice have been generated by crossing CAST/EiJ with C57BL/6 to overcome this problem of MAIT cell paucity, although the effect on disease remains unknown (Cui et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Mice generated with induced pluripotent stem cells derived from mucosal-associated invariant T cells

Sugimoto

Fujita

Wakao

2022

Preprint

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The function of mucosal-associated invariant T (MAIT) cells, a burgeoning family of innate-like T cells abundant in humans and implicated in many diseases, remains obscure. To explore this, mice with a rearranged T cell receptor (TCR) α or β locus, specific for MAIT cells, were generated via induced pluripotent stem cells derived from MAIT cells and designated Vα19 and Vβ8 mice, respectively. Both mice expressed large amounts of MAIT cells. The MAIT cells from these mice were activated by cytokines and an agonist to produce IFN-γ and IL-17. While Vβ8 mice showed resistance in a cancer metastasis model, V α19 mice did not. Adoptive transfer of MAIT cells from the latter into the control mice, however, recapitulated the resistance. This has implications for understanding the role of MAIT cells in health and disease and in developing treatments for the plethora of diseases in which MAIT cells are implicated.

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“…In different models of infection, providing activating MAIT cells together with the administration of specific vaccines shows a significant adjuvant effect, i.e. increases vaccine immunogenicity (52)(53)(54). Cancer vaccines often lack immunogenicity and therefore could possibly benefit from this approach, as already shown for NKT cells (55)(56)(57).…”

Section: Mait Cells As Adjuvants For Vaccine Immunologymentioning

confidence: 99%

Mucosal-associated invariant T cells in hematological malignancies: Current knowledge, pending questions

Treiner

2023

Front. Immunol.

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Non-classical HLA restricted T cell subsets such as γδ T and NK-T cells are showing promises for immune-based therapy of hematological malignancies. Mucosal-Associated Invariant T cells (MAIT) belong to this family of innate-like T cell subsets and are the focus of many studies on infectious diseases, owing to their unusual recognition of bacterial/fungal metabolites. Their ability to produce type 1 cytokines (IFNγ, TNFα) as well as cytotoxic effector molecules endows them with potential anti-tumor functions. However, their contribution to tumor surveillance in solid cancers is unclear, and only few studies have specifically focused on MAIT cells in blood cancers. In this review, we wish to recapitulate our current knowledge on MAIT cells biology in hematological neoplasms, at diagnosis and/or during treatment, as well as tentative approaches to target them as therapeutic tools. We also wish to take this opportunity to briefly elaborate on what we think are important question to address in this field, as well as potential limitations to overcome in order to make MAIT cells the basis of future, novel therapies for hematological cancers.

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Augmentation of the Riboflavin-Biosynthetic Pathway Enhances Mucosa-Associated Invariant T (MAIT) Cell Activation and Diminishes Mycobacterium tuberculosis Virulence

Cited by 20 publications

References 100 publications

The intracellular pathogen Francisella tularensis escapes from adaptive immunity by metabolic adaptation

The intracellular pathogen Francisella tularensis escapes from adaptive immunity by metabolic adaptation

Mice generated with induced pluripotent stem cells derived from mucosal-associated invariant T cells

Mucosal-associated invariant T cells in hematological malignancies: Current knowledge, pending questions

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