Navigating the gastric frontier of mucosal immunity against Helicobacter pylori

Helicobacter pylori (H. pylori) is a globally prevalent bacterium that causes chronic infection and, while often asymptomatic, is a major cause of gastritis, peptic ulcer disease, and a risk factor for gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Infection triggers robust innate and adaptive immune responses in the gastric mucosa, including immune cell recruitment and pro-inflammatory cytokine production; however, the bacterium frequently persists by evading host immunity through mechanisms such as CagA-mediated epithelial damage and modulation of heat shock proteins. This review examines the interplay between mucosal immunity and H. pylori, with a particular focus on the unique functional roles of mucosa-associated invariant T (MAIT) cells in orchestrating host defense. We also explore therapeutic strategies that leverage mucosal immunity to combat H. pylori, including immune-based interventions to eradicate infection and approaches targeting H. pylori-associated diseases, such as gastric cancer, autoimmune disorders, and peptic ulcer disease.