Helicobacter pylori infection: mechanism of colonization and functional dyspepsia Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin-10

J Gastroenterol Hepatol. 2001 Apr;16(4):377-83. doi: 10.1046/j.1440-1746.2001.02459.x.

Abstract

Background and aims: Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine. Mice deficient in IL-10 production (IL-10-/-mice) develop a spontaneous chronic enterocolitis, suggesting that IL-10 is an important regulator of the mucosal immune response in vivo. The objective of this study was to determine the role of endogenous IL-10 in the host defense against gastric colonization by Helicobacter pylori by using IL-10-deficient mice.

Methods: The IL-10-/-mice were inoculated intragastrically with a mouse-adapted H. pylori isolate (Sydney Strain 1). Gastric colonization by H. pylori (biopsy urease test and bacterial colony counts), serum levels of H. pylori-specific immunoglobulin (Ig) M, A, G, isotypes of IgG, and the gastric mucosal inflammatory scores were determined 6 weeks after inoculation. Results were compared with those obtained from H. pylori-infected control mice (IL-10+/-mice).

Results: The colonization of gastric mucosa by H. pylori was reduced approximately 100-fold (P < 0.0001) in IL-10-/-mice (log10 4.87 +/- 0.26CFU/g tissue) as compared to IL-10+/-mice (log10 6.64 +/- 0.22 CFU/g tissue). Furthermore, IL-10-/-mice infected with H. pylori had significantly higher H. pylori-specific IgA and IgG antibodies in serum (P < or = 0.01), and developed much more severe chronic active gastritis than infected IL-10+/-mice. The median scores of the infiltration of gastric mucosa by mononuclear cells and neutrophils were up to threefold higher in IL-10-/-mice than they were in IL-10+/-mice.

Conclusion: Our studies suggest that endogenous IL-10 is an inhibitor of the protective immune response to H. pylori infection. Interleukin-10 participates in the downregulation of H. pylori-induced gastric inflammatory responses, which apparently confers a survival advantage to the organism promoting more effective colonization of gastric mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / analysis
  • Gastric Mucosa / microbiology*
  • Gastritis / microbiology
  • Gastritis / pathology
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / immunology
  • Helicobacter pylori / physiology*
  • Interleukin-10 / deficiency*
  • Interleukin-10 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout / genetics
  • Stem Cells / physiology

Substances

  • Antibodies, Bacterial
  • Interleukin-10