Deficiency of the myeloid differentiation primary response molecule MyD88 leads to an early and rapid development of Helicobacter-induced gastric malignancy

Infect Immun. 2014 Jan;82(1):356-63. doi: 10.1128/IAI.01344-13. Epub 2013 Oct 28.


Approximately 50% of the world's population is infected with Helicobacter pylori, leading to chronic inflammation, which increases the risk for gastric adenocarcinoma. MyD88 is a key adaptor molecule in inflammatory pathways involved in interleukin 1 (IL-1)/IL-18/Toll-like receptor signaling and has been shown to have divergent effects in carcinogenesis. The role of MyD88 in Helicobacter-induced gastric malignancy is unknown. Using a mouse model of Helicobacter-induced gastric cancer, we assessed the role of MyD88 in cancer development by evaluating gastric histopathology, apoptosis, proliferation, and cytokine expression. Infection of MyD88-deficient (Myd88(-/-)) mice with Helicobacter resulted in early and rapid advancement to gastric dysplasia as early as 25 weeks postinfection. The progression of Helicobacter-induced disease to precancerous and cancerous lesions in the absence of MyD88 signaling was accompanied by increased gastric epithelial apoptosis and proliferation. In addition, inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), IL-6, and IL-1β were highly expressed in association with the development of gastric dysplasia. These data suggest that MyD88 signaling retards development and progression to cancer during Helicobacter infection. This is the first study to show evidence of MyD88 protection in an infection-driven inflammation-associated cancer model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Proliferation
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Epithelial Cells / cytology
  • Gastric Mucosa / cytology
  • Gene Expression Regulation, Bacterial
  • Helicobacter Infections / complications*
  • Helicobacter pylori* / genetics
  • Immunologic Deficiency Syndromes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / physiology*
  • Precancerous Conditions / microbiology
  • Precancerous Conditions / pathology
  • Primary Immunodeficiency Diseases
  • Stomach Neoplasms / microbiology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / physiopathology


  • Cytokines
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88

Supplementary concepts

  • MYD88 Deficiency