Immune Evasion Mechanisms of H. pylori

The gastric epithelial barrier, composed of physical, chemical, cellular barriers, and immune auxiliary components, constitutes the core multilayered defense system of the gastric mucosa against gastric acid, pepsin, and external harmful substances. Its main components and functions are as follows: (1) The mucus-bicarbonate-phospholipid barrier: The gastric mucosal surface is covered by a thick mucus layer composed of glycoproteins, which lubricates food and slows gastric acid penetration [1, 2]. Bicarbonate embedded in the mucus is actively secreted by gastric mucosal epithelial cells, forming a pH gradient (near the epithelium pH ~7.0, away from the epithelium pH ~1.0), neutralizing gastric acid and inhibiting pepsin activity [3]; furthermore, phospholipid molecules enhance the barrier’s acid resistance through hydrophobic interactions [4]. (2) Epithelial cells and tight junctions: The gastric mucosal epithelium consists of a single layer of columnar cells, forming a seamless physical barrier through tight junction proteins, preventing H+ back-diffusion into the submucosa [5]. These cells renew rapidly (renewal cycle ~3–5 days), enabling timely repair of damaged areas [6]. (3) Ion channels and immune regulation: The chloride ion channel Slc26a9 is highly expressed in gastric epithelial cells, reducing epithelial cell death and maintaining barrier stability by regulating endoplasmic reticulum stress and mitochondrial-dependent apoptotic signaling [7]. Additionally, alarmins secreted by epithelial cells can activate immune cells [8], and secreted defensins can directly kill bacteria and viruses, reducing microbial damage to the barrier [9]. The gastric epithelial barrier is the host’s first line of defense against Helicobacter pylori. By disrupting this barrier, H. pylori can not only breach the host’s initial defense and achieve colonization but also indirectly interfere with subsequent immune responses, creating a safe colonization microenvironment for itself.