Inflammation promotes stomach epithelial defence by stimulating the secretion of antimicrobial peptides in the mucus

Mucus is a protein-based gel secreted by specialized epithelial cells that protects the gastrointestinal mucosa from microorganism attack and irritating agents. Experiments in mice have demonstrated that when the mucosa is infected or inflamed, the mucus becomes enriched with broad-spectrum bactericidal compounds known as antimicrobial peptides (AMPs). Although AMP gene expression has been identified in both immune and epithelial cells, how inflammation regulates AMP secretion in the mucus remains unclear, and the efficacy of AMP-enriched mucus in defending against microorganisms has not been assessed. We have developed a “mucosoid” culture model that simulates the healthy human stomach epithelium. In these cultures, epithelial cells form a barrier and can differentiate into mucus-secreting cells. The accumulation of mucus on the apical side facilitates the detection of AMPs and the assessment of their bactericidal properties. We report that cytokines TNFa, IL1b and IFNg enhance the secretion of the AMPs lactotransferrin, lipocalin2, C3A, and CXCL9 into the mucus. The mucus from inflamed cells which contains the aforementioned AMPs partially kills Helicobacter pylori, the sole stomach pathogen. However, H. pylori can inhibit this defence by reducing AMP gene expression in inflamed epithelial cells. These results reveal that secreted mucus is a relevant effector of epithelial immunity but pathogens like H. pylori can subvert these defences to persist in the mucosa. Trascriptomic profile of gastric mucosoids treated with TNFɑ, IL1β and IFNɣ and with every single cytokine were analyzed and compared to non treated samples on Agilent-8x60k Human custom arrays as single-color hybridizations.