What is the immune-mediated response in Helicobacter pylori (H. pylori) infection?

Immune-Mediated Response in Helicobacter pylori Infection

H. pylori infection triggers a complex immune response characterized by both innate and adaptive components, resulting in chronic inflammation that fails to eliminate the bacterium while causing tissue damage. 1

Innate Immune Response

• Pattern Recognition: H. pylori is recognized by innate immune receptors, though the bacterium can modify its surface molecules to partially evade detection 1

• NOD1 Activation: An important component of innate immunity against H. pylori involves NOD1, an intracellular sensor that detects peptidoglycan fragments from bacterial cell walls 2

  • NOD1 signaling generates type I interferons that regulate chemokine and cytokine responses affecting infection severity 2

• Macrophage and Mast Cell Alterations:

  • Altered numbers of resident macrophages in the intestinal mucosa 3
  • Increased mast cells surrounding nerve fibers, which correlates with abdominal symptoms 3

Adaptive Immune Response

• T Cell Response:

  • Increased lamina propria T lymphocytes and epithelial T cell counts 3
  • Higher frequency of activated/memory CD45+ T cells 3
  • Complex mix of Th1, Th17, and Treg responses 4
  • The balance between these T cell subsets may determine clinical outcomes 4

• B Cell Response:

  • Decreased frequency of B cells in colonic lamina propria 3
  • Production of antibodies against bacterial components, including flagellin antigens 3
  • Host antibodies to Cytolethal distending toxin B (CdtB) can cross-react with vinculin 3

• Cytokine Dysregulation:

  • Increased mucosal IL-1β mRNA expression 3
  • Elevated IFN-γ and decreased IL-10 levels, suggesting Th1/Th2 imbalance 3
  • Reduced IL-13 (Th2 cytokine) release from mucosal biopsies 3

Bacterial Evasion Mechanisms

• Immune Subversion: H. pylori can escape, disrupt, and manipulate host immune responses 1

  • Alters surface molecules to avoid recognition by innate immune receptors 1
  • Modulates effector T cell responses 1
  • Induces regulatory T-cell responses that contribute to bacterial persistence 5

• Microbiota Interaction:

  • H. pylori infection can lead to dysbiosis 3
  • Lymphocyte frequencies in epithelial lining and lamina propria negatively correlate with mucosal microbial diversity 3

Pathophysiological Consequences

• Intestinal Permeability: Increased intestinal permeability persists in chronic infection, associated with low-grade immune activation 3

• Enteroendocrine Changes:

  • Increased colonic enterochromaffin cell counts, positively correlated with CD3 T cell counts 3
  • Elevated serotonin (5-HT) containing cells and Peptide YY (PYY) containing cells 3

• Genetic Factors:

  • Variants in TLR9 (pattern recognition receptor), IL6 (pro-inflammatory cytokine), and CDH1 (tight junction protein) may influence susceptibility 3

Clinical Implications

• The immune response to H. pylori is paradoxical - it's both protective and damaging to the host 6
• The chronic inflammation contributes to gastritis, peptic ulcers, MALT lymphoma, and gastric adenocarcinoma 1
• Despite strong immune activation, the infection typically persists lifelong without antibiotic treatment 5
• The relative balance of Th1, Th17, and Treg responses likely influences disease outcomes 4

Vaccination strategies targeting H. pylori have shown promise in animal models but developing effective human vaccines has proven difficult due to the bacterium's complex immunomodulatory properties 5.