Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Mucosa-associated invariant T (MAIT) cells are a unique population of αβ T cells in mammals that reside preferentially in mucosal tissues and express an invariant Vα paired with limited Vβ T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Using<jats:italic>in vitro</jats:italic>assays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens. However, whether MAIT cells play an important, and perhaps unique, role in controlling microbial infection has remained unclear. To probe MAIT cell function, we show here that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Mycobacterium bovis</jats:named-content>BCG in macrophages (MΦ) in coculture assays, and this inhibitory activity was dependent upon MAIT cell selection by MR1, secretion of gamma interferon (IFN-γ), and an innate interleukin 12 (IL-12) signal from infected MΦ. Surprisingly, however, the cognate recognition of MR1 by MAIT cells on the infected MΦ was found to play only a minor role in MAIT cell effector function. We also report that MAIT cell-deficient mice had higher bacterial loads at early times after infection compared to wild-type (WT) mice, demonstrating that MAIT cells play a unique role among innate lymphocytes in protective immunity against bacterial infection.</jats:p>

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

“…Activated peripheral MAIT cells produce large quantities of IFN-g and TNF-a but also possess a Th17-signature profile, because they release IL-17A after mitogen stimulation and express the Th17-associated transcription factor RORC and the Th17-related chemokine receptor CCR6 (16,17). The functional and developmental profile of MAIT cells, together with their preferential localization in the vascular bed of the gut and liver, indicate that MAIT cells may play a major role in controlling the dissemination of pathogens that could escape the gut mucosal barrier (19) or be implicated in liver pathological processes of different etiologies (20). However, the objective difficulties in obtaining samples from human parenchymal organs, particularly in nonpathological situations, have hampered the functional characterization of MAIT cells from the human liver.…”

Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

“…A recent study indicated that MAIT cells recognize riboflavin (vitamin B2) derivatives in an MHC class 1b-like related protein (MR1)-dependent manner (7). After Ag recognition, MAIT cells rapidly produce Th1/Th17 cytokines, such as IFN-g and IL-17, in an innate-like manner (6), and they contribute to protection against certain mycobacterial and enterobacterial infections (3,4,(8)(9)(10).…”

Mucosal associated invariant T cells: Don't forget your vitamins

“…Finally, the preferential localization of MAIT cells in the lining of mucosal surfaces and their protective role in several infections [8,9,13,14] …”