Role of MAIT cells in gastrointestinal tract bacterial infections in humans: More than a gut feeling

Zheng, Yi-Chao; Han, Fei; Ho, Amanda; Xue, Yiting; Wu, Zhenzhou; Chen, X; Sandberg, Johan K.; Ma, Shaohua; Leeansyah, Edwin

doi:10.1016/j.mucimm.2023.06.005

Cited by 6 publications

(8 citation statements)

References 176 publications

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“…provide a comprehensive review on MAIT cells in gastrointestinal bacterial infections, revealing their intricate roles. They emphasize recent findings, showcasing the dynamic nature of MAIT cell responses, which vary based on etiological agents and anatomical locations ( 42 ). MAIT cells can also improve bacterial control during chronic infection and reduce bacterial loads through IL-17A-dependent mechanisms ( 26 , 43 ).…”

Section: Mait Cells During Infectious Diseasessupporting

confidence: 64%

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

Yigit,

Basoglu,

Unutmaz

2024

Front. Immunol.

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Mucosal-associated invariant T (MAIT) cells play diverse roles in cancer, infectious diseases, and immunotherapy. This review explores their intricate involvement in cancer, from early detection to their dual functions in promoting inflammation and mediating anti-tumor responses. Within the solid tumor microenvironment (TME), MAIT cells can acquire an ‘exhausted’ state and secrete tumor-promoting cytokines. On the other hand, MAIT cells are highly cytotoxic, and there is evidence that they may have an anti-tumor immune response. The frequency of MAIT cells and their subsets has also been shown to have prognostic value in several cancer types. Recent innovative approaches, such as programming MAIT cells with chimeric antigen receptors (CARs), provide a novel and exciting approach to utilizing these cells in cell-based cancer immunotherapy. Because MAIT cells have a restricted T cell receptor (TCR) and recognize a common antigen, this also mitigates potential graft-versus-host disease (GVHD) and opens the possibility of using allogeneic MAIT cells as off-the-shelf cell therapies in cancer. Additionally, we outline the interactions of MAIT cells with the microbiome and their critical role in infectious diseases and how this may impact the tumor responses of these cells. Understanding these complex roles can lead to novel therapeutic strategies harnessing the targeting capabilities of MAIT cells.

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Section: Mait Cells During Infectious Diseasessupporting

confidence: 64%

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

Yigit,

Basoglu,

Unutmaz

2024

Front. Immunol.

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“…In peripheral blood, MAIT abundance ranges from ∼1 – 10% of T cells 31 . As their name implies, MAIT cells also localize to body barriers and tissues, with an abundance of ∼20 – 40% in the liver 31 , 1.2-2.5% in the gut ileum, and 1-10% in the colon 32 .…”

Section: Introductionmentioning

confidence: 99%

Seq2MAIT: A Novel Deep Learning Framework for Identifying Mucosal Associated Invariant T (MAIT) Cells

ElAbd,

Byron,

Woodhouse

et al. 2024

Preprint

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Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells that mainly recognize bacterial vitamin B metabolites presented on MHC-related protein 1 (MR1). MAIT cells have been shown to play an important role in controlling bacterial infection and in responding to viral infections. Furthermore, MAIT cells have been implicated in different chronic inflammatory diseases such as inflammatory bowel disease and multiple sclerosis. Despite their involvement in different physiological and pathological processes, a deeper understanding of MAIT cells is still lacking. Arguably, this can be attributed to the difficulty of quantifying and measuring MAIT cells in different biological samples which is commonly done using flow cytometry-based methods and single-cell-based RNA sequencing techniques. These methods mostly require fresh samples which are difficult to obtain, especially from tissues, have low to medium throughput, and are costly and labor-intensive. To address these limitations, we developed sequence-to-MAIT (Seq2MAIT) which is a transformer-based deep neural network capable of identifying MAIT cells in bulk TCR-sequencing datasets, enabling the quantification of MAIT cells from any biological materials where human DNA is available. Benchmarking Seq2MAIT across different test datasets showed an average area-under-the-receiver-operator-curve (AU[ROC]) >0.80. In conclusion, Seq2MAIT is a novel, economical, and scalable method for identifying and quantifying MAIT cells in virtually any biological sample.

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“…Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved innate-like T cell population abundant in the human blood and barrier tissues, including the gastrointestinal tract [reviewed in ( 1 , 2 )]. Human MAIT cells are defined by their semi-invariant T cell receptor (TCR) usage and recognize microbial metabolite antigens presented by the major histocompatibility complex related 1 (MR1) molecule ( 1 , 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Human MAIT cells are also identifiable through their expression of TCR Vα7.2 combined with high levels of the C-type lectin CD161 ( 14 – 16 ). MAIT cells mediate antimicrobial immunity by eliciting type 1, type 17, cytotoxic, and innate-like effector responses within the gastrointestinal tract ( 1 , 2 ). MAIT cells respond to riboflavin-producing microbes via a combination of MR1/TCR-dependent and cytokine-dependent pathways and release cytolytic proteins and antimicrobial cytokines to kill both intracellular and extracellular bacteria and orchestrate adaptive immune responses ( 14 , 17 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

“…Circulating MAIT cells express high levels of gut-homing and inflammation-associated chemokine receptors, including CCR2, CCR5, CCR6, CCR9, and CXCR6 ( 14 , 27 – 30 ), as well as tissue-homing molecules including α4β1, α4β7, αΕβ7, and αLβ2 integrins ( 12 , 24 , 28 , 31 – 36 ). However, although MAIT cells are implicated in the setting of acute intestinal infections and inflammation, there is no conclusive evidence for their trafficking to the gut or mechanisms by which this may occur ( 2 , 37 – 47 ). In addition, many of these studies were conducted using circulating MAIT cell samples [reviewed in ( 2 )].…”

Section: Introductionmentioning

confidence: 99%

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MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis

Zheng,

Han,

et al. 2024

Sci. Adv.

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Mucosal-associated invariant T (MAIT) cells are antimicrobial T cells abundant in the gut, but mechanisms for their migration into tissues during inflammation are poorly understood. Here, we used acute pediatric appendicitis (APA), a model of acute intestinal inflammation, to examine these migration mechanisms. MAIT cells were lower in numbers in circulation of patients with APA but were enriched in the inflamed appendix with increased production of proinflammatory cytokines. Using the patient-derived appendix organoid (PDAO) model, we found that circulating MAIT cells treated with inflammatory cytokines elevated in APA up-regulated chemokine receptors, including CCR1, CCR3, and CCR4. They exhibited enhanced infiltration of Escherichia coli –pulsed PDAO in a CCR1-, CCR2-, and CCR4-dependent manner. Close interactions of MAIT cells with infected organoids led to the PDAO structural destruction and death. These findings reveal a previously unidentified mechanism of MAIT cell tissue homing, their participation in tissue damage in APA, and their intricate relationship with mucosal tissues during acute intestinal inflammation in humans.

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Role of MAIT cells in gastrointestinal tract bacterial infections in humans: More than a gut feeling

Cited by 6 publications

References 176 publications

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

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

Seq2MAIT: A Novel Deep Learning Framework for Identifying Mucosal Associated Invariant T (MAIT) Cells

MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis

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