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Link to original content: https://pubmed.ncbi.nlm.nih.gov/26136743
MR1-Restricted Mucosal-Associated Invariant T Cells and Their Activation during Infectious Diseases - PubMed Skip to main page content
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Review
. 2015 Jun 16:6:303.
doi: 10.3389/fimmu.2015.00303. eCollection 2015.

MR1-Restricted Mucosal-Associated Invariant T Cells and Their Activation during Infectious Diseases

Lauren J Howson  1 , Mariolina Salio  1 , Vincenzo Cerundolo  1
Affiliations
Review

MR1-Restricted Mucosal-Associated Invariant T Cells and Their Activation during Infectious Diseases

Lauren J Howson et al. Front Immunol. .

Abstract

MR1-restricted mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites, which are generated by a broad range of bacteria, from Escherichia coli to Mycobacterium tuberculosis and BCG. MAIT cells have been described as innate sensors of infection as they accumulate early in infected tissues. MAIT cells maintain an activated phenotype throughout the course of infections, secrete inflammatory cytokines, and have the potential to directly kill infected cells, playing an important role in shaping the host response. In this review, we will discuss the current knowledge regarding the molecular mechanisms that underline MAIT cells activation in sterile and non-sterile inflammatory conditions.

Keywords: MAIT cells; MR1; bacteria; infection; vitamins.

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Figures

Figure 1
Figure 1
Proposed mechanisms of MAIT cell activation in infection and sterile disease. Bacteria or yeast (1) can stimulate MAIT cell activation following infection or phagocytosis by antigen presenting cells. These cells can then present microbial-derived vitamin B metabolites via MR1 (associated with β2-microglobulin) to the Vα7.2-bearing MAIT TCR. Upon infection, antigen presenting cells also produce IL-12 and IL-18 cytokines that can activate MAIT cells in an antigen-independent mechanism. The production of IL-7 from hepatocytes can act synergistically to enhance MAIT cell activation. Viruses (2) can stimulate MAIT cells through detection of their molecular patterns by pattern recognition receptors, such as ssRNA by TLR8 on antigen presenting cells, resulting in the production of IL-12 and IL-18. In sterile disease (3), such as autoimmunity, cells that pathologically express cytokines IL-12 and IL-18 can activate MAIT cells. The activation of MAIT cells (4) results in the production of Th1 cytokines IFNγ and TNFα, Th17 cytokines IL-17 and IL-22 (particularly by small intestine-derived MAIT cells), and release of perforin and granzyme B to directly kill infected cells.
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