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Cited by 150Alcohol Consumption and Health EffectsT-cell and B-cell ImmunologyGut microbiota and health

Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease

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Riva, Antonio, Patel, Vishal, Kurioka, Ayako, Jeffery, Hannah C, Wright, Gavin, Tarff, Sarah, Shawcross, Debbie, Ryan, Jennifer M +16 more·2018·Gut
DOI 10.1136/gutjnl-2017-314458PMC PMC5890654
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Abstract

Background/aims: Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown. Methods/design: We analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively. Results: In ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments. Conclusions: In ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the ‘leaky’ gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients.

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  • The crucial role of MAIT cells as liver sentinels against bacteria is suggested by the effect of their dysfunction in alcoholic liver disease, which increases greatly the susceptibility of these patients to liver infections.

    “The crucial role 446 of MAIT cells as liver sentinels against bacteria is suggested by the effect of their 447 dysfunction in alcoholic liver disease, which increases greatly the susceptibility of these 448 patients to liver infections(90, 91).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [90]

    The Discussion (page unavailable) reports greater acquired bacterial infection in patients with severe alcoholic hepatitis, who also had the strongest MAIT-cell loss and dysfunction. It proposes that MAIT-cell defects may contribute to infection susceptibility and describes a possible protective role in the liver. It does not establish that the dysfunction greatly increases susceptibility or that the infections were specifically liver infections. (LLM, conf=0.87)

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Authors
Riva, A., Patel, V., Kurioka, A., Jeffery, H. C., Wright, G., Tarff, S., Shawcross, D., Ryan, J. M., Evans, A., Azarian, S., Bajaj, J. S., Fagan, A., Patel, V., Mehta, K., Lopez, C., Simonova, M., Katzarov, K., Hadzhiolova, T., Pavlova, S., Wendon, J. A., Oo, Y. H., Klenerman, P., Williams, R., & Chokshi, S.
Affiliations
  • King's College London (GB)
  • University of Oxford (GB)
  • University of Birmingham (GB)
  • Basildon Hospital (GB)
  • Royal Berkshire Hospital (GB)
  • Foundation for Liver Research (GB)
  • Virginia Commonwealth University (US)
  • University of Westminster (GB)
  • Military Medical Academy (BG)
Corresponding author
Chokshi, Shilpa
ORCID
Venue
Gut
Publisher
BMJ
Published
2017-11-02
Volume
67
Issue
5
Pages
918-930
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gutjnl-2017-314458
PMC
PMC5890654
OpenAlex
W2765152120
Cited by
150
References
1
Citations by year
2026: 6 · 2025: 17 · 2024: 15 · 2023: 18 · 2022: 25 · 2021: 21 · 2020: 22 · 2019: 17 · 2018: 8 · 2017: 1
FWCI
10.31
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Gut (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Research Open (London South Bank University) (acceptedVersion)
  • WestminsterResearch (University of Westminster) (acceptedVersion)
  • Research Open (London South Bank University) (acceptedVersion, cc-by-nc)
  • WestminsterResearch (University of Westminster) (acceptedVersion, cc-by-nc)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc)
  • Research Portal (King's College London) (submittedVersion, cc-by-nc)
  • Lund University Publications (Lund University) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Foundation for Liver Research
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
mucosal-associated invariant T cells, alcoholic liver disease, alcoholic hepatitis, alcoholic cirrhosis, intestinal permeability, microbial translocation, intestinal immunity, antibacterial immunity, T cell dysfunction, fecal bacteria, gut microbiota, ethanol, homing receptors, transcriptional regulation, infection susceptibility
MeSH terms
Mucosal-Associated Invariant T Cells, Adult, Ethanol, Feces, Female, Humans, Immunohistochemistry, Intestinal Mucosa, Liver Diseases, Alcoholic, Male, Middle Aged, Cytokines, Cell Culture Techniques, Gene Expression Profiling, Real-Time Polymerase Chain Reaction

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