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MAIT cells: a novel therapeutic target for alcoholic liver disease?
  1. Bin Gao,
  2. Jing Ma,
  3. Xiaogang Xiang
  1. Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Dr Bin Gao, Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA; bgao{at}mail.nih.gov

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Bacterial infection is one of the most frequent and severe complications of advanced alcoholic liver disease (ALD), including alcoholic cirrhosis and severe alcoholic hepatitis (SAH). Patients who suffered from SAH are susceptible to bacterial infection with one study reporting 50% of them developed bacterial infection.1 Additionally, standard corticosteroid treatment further increased the risk of bacterial infection in patients with SAH.1 Thus, infection is highly relevant for the outcome of SAH and represents an important therapeutic target. However, except antibiotic treatment, there are currently no other specific therapies that effectively control bacterial infection in SAH due to incomplete understanding of the pathogenesis of bacterial infection in these patients.

The mechanisms underlying the increased risk of bacterial infection in ALD are complex and multifactorial. The high incidence of bacterial infection may be partly explained by gut bacterial overgrowth, dysbiosis and translocation of gut bacteria and their products in patients with ALD.2 3 Impaired host defence against bacterial infection is probably another important mechanism contributing to the increased risk of bacterial infection in patients with ALD. It has been well documented that excessive alcohol consumption has broad and significant inhibitory effects on many key components of the immune system. For example, neutrophils, the first cellular line of defence against microorganisms, have impaired functions in patients with SAH, such as weakened reactive oxygen species production, reduced exocytosis/phagocytosis, declined chemotaxis and severe bactericidal defect.4 T cells from patients with SAH, but not alcoholic cirrhosis, expressed elevated levels of inhibitory mediators (eg, programmed cell death 1, PD ligand 1) that markedly inhibited T cell functions against bacterial infection.4 Although many types …

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Footnotes

  • Contributors BG, JM and XX wrote the paper. BG and JM made the figure. BG supervised to write the paper.

  • Funding This study was funded by the National Institute on Alcohol Abuse and Alcoholism (Intramural programme).

  • Competing interests Bin Gao is a US Federal Government employee acting in the course of his employment.

  • Provenance and peer review Commissioned; internally peer reviewed.

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