Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role in Helicobacter pylori Infection

Abstract

Mucosal-associated invariant T (MAIT) cells represent a class of antimicrobial innate-like T cells that have been characterized in human blood, liver, lungs, and intestine. Here, we investigated, for the first time, the presence of MAIT cells in the stomach of children, adults, and the elderly undergoing routine endoscopy and assessed their reactivity to Helicobacter pylori (H. pylori – Hp), a major gastric pathogen. We observed that MAIT cells are present in the lamina propria compartment of the stomach and display a similar memory phenotype to blood MAIT cells. We then demonstrated that gastric and blood MAIT cells are able to recognize H. pylori. We found that CD8+ and CD4−CD8− (double negative) MAIT cell subsets respond to H. pylori-infected macrophages stimulation in a MR-1 restrictive manner by producing cytokines (IFN-γ, TNF-α, IL-17A) and exhibiting cytotoxic activity. Interestingly, we observed that blood MAIT cell frequency in Hp+ve individuals was significantly lower than in Hp−ve individuals. However, gastric MAIT cell frequency was not significantly different between Hp+ve and Hp−ve individuals, demonstrating a dichotomy between blood and gastric tissues. Further, we observed that the majority of gastric MAIT cells (>80%) expressed tissue-resident markers (CD69+ CD103+), which were only marginally present on PBMC MAIT cells (<3%), suggesting that gastric MAIT cells are readily available to respond quickly to pathogens. These results contribute important new information to the understanding of MAIT cells function on peripheral and mucosal tissues and its possible implications in the host response to H. pylori.

Loss of Circulating Mucosal-Associated Invariant T Cells in Common Variable Immunodeficiency Is Associated with Immune Activation and Loss of Eomes and PLZF

“…Loss of MAIT cells has also been reported in cystic fibrosis (45), a genetic condition associated with chronic bacterial infections. Similarly, individuals carrying Helicobacter pylori, with mycobacterial infections, or patients with severe bacterial infection have lower blood MAIT cells (46)(47)(48). Overall, this suggests that the loss of MAIT cells in CVID and other diseases could reflect the infection burden.…”

Challenge of Humans with Wild-type Salmonella enterica Serovar Typhi Elicits Changes in the Activation and Homing Characteristics of Mucosal-Associated Invariant T Cells

“…Briefly, after overnight (16–18 h) resting at 37°C, 5% CO 2 , PBMC were harvested, stained with a dead-cell discriminator, yellow fluorescent viability dye (YEVID, Invitrogen, Carlsbad, CA, USA) (16), followed by surface staining with mAbs against caspase-3, CCR6, CCR9, CD3, CD4, CD8, CD14, CD19, CD38, CD57, CD161, HLA-DR, and TCRα 7.2 surface antigens and fixation and permeabilization with Fix & Perm cell buffers (Invitrogen, Carlsbad, CA, USA) (12, 16). Cells were then stained intracellularly for Ki67.…”

Review: Helicobacter: Inflammation, immunology, and vaccines

“…MAIT cells can have both detrimental and beneficial effects for the host during infection but, in the case of H pylori-infected mice, these cells appeared to promote gastritis. 25 Further studies are required to fully define the role of MAIT cells in H pylori-induced inflammation. In contrast, Mr1 −/− mice lacking MAIT cells showed significantly less gastric pathology.…”