Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children

Mucosal Immunol. 2013 Sep;6(5):950-959. doi: 10.1038/mi.2012.133. Epub 2013 Jan 9.

Abstract

Helicobacter pylori induces less gastric inflammation in children than adults. Here we investigated whether this reduced inflammation involves dysregulated T helper type 17 (Th17) responses. H. pylori-infected children and adults in Santiago, Chile had similar levels of H. pylori colonization, proportions of bacteria containing cagA and s1/s2 vacA markers of virulence, and strain genotypes (predominantly hpEurope), but the children had significantly reduced levels of gastric inflammation and neutrophil infiltration. The reduced neutrophil accumulation in the infected children was accompanied by significantly fewer gastric Th17 cells and significantly lower levels of interleukin (IL)-17-specific mRNA and protein compared with the infected adults. The gastric mucosa of H. pylori-infected children also contained higher numbers of IL-10+ cells and increased levels of both IL-10 and Foxp3 mRNA compared with that of the infected adults. Thus, reduced gastric inflammation, including diminished neutrophil accumulation, in H. pylori-infected children compared with infected adults is likely due to downregulated gastric Th17/IL-17 responses as a consequence of enhanced mucosal regulatory T-cell activity in the children.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gastric Mucosa / immunology*
  • Gastritis / etiology
  • Gastritis / immunology*
  • Gene Expression Regulation
  • Helicobacter Infections / complications
  • Helicobacter Infections / immunology*
  • Helicobacter pylori / immunology*
  • Helicobacter pylori / pathogenicity
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Male
  • Middle Aged
  • Neutrophils / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*
  • Virulence Factors

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Virulence Factors
  • Interleukin-10