Coinfection with Enterohepatic Helicobacter species can ameliorate or promote Helicobacter pylori-induced gastric pathology in C57BL/6 mice

Infect Immun. 2011 Oct;79(10):3861-71. doi: 10.1128/IAI.05357-11. Epub 2011 Jul 25.

Abstract

To investigate how different enterohepatic Helicobacter species (EHS) influence Helicobacter pylori gastric pathology, C57BL/6 mice were infected with Helicobacter hepaticus or Helicobacter muridarum, followed by H. pylori infection 2 weeks later. Compared to H. pylori-infected mice, mice infected with H. muridarum and H. pylori (HmHp mice) developed significantly lower histopathologic activity index (HAI) scores (P < 0.0001) at 6 and 11 months postinoculation (MPI). However, mice infected with H. hepaticus and H. pylori (HhHp mice) developed more severe gastric pathology at 6 MPI (P = 0.01), with a HAI at 11 MPI (P = 0.8) similar to that of H. pylori-infected mice. H. muridarum-mediated attenuation of gastritis in coinfected mice was associated with significant downregulation of proinflammatory Th1 (interlukin-1beta [Il-1β], gamma interferon [Ifn-γ], and tumor necrosis factor-alpha [Tnf-α]) cytokines at both time points and Th17 (Il-17A) cytokine mRNA levels at 6 MPI in murine stomachs compared to those of H. pylori-infected mice (P < 0.01). Coinfection with H. hepaticus also suppressed H. pylori-induced elevation of gastric Th1 cytokines Ifn-γ and Tnf-α (P < 0.0001) but increased Th17 cytokine mRNA levels (P = 0.028) at 6 MPI. Furthermore, mRNA levels of Il-17A were positively correlated with the severity of helicobacter-induced gastric pathology (HhHp>H. pylori>HmHp) (at 6 MPI, r² = 0.92, P < 0.0001; at 11 MPI, r² = 0.82, P < 0.002). Despite disparate effects on gastritis, colonization levels of gastric H. pylori were increased in HhHp mice (at 6 MPI) and HmHp mice (at both time points) compared to those in mono-H. pylori-infected mice. These data suggest that despite consistent downregulation of Th1 responses, EHS coinfection either attenuated or promoted the severity of H. pylori-induced gastric pathology in C57BL/6 mice. This modulation was related to the variable effects of EHS on gastric interleukin 17 (IL-17) responses to H. pylori infection.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Down-Regulation
  • Female
  • Gastric Mucosa / pathology
  • Gastritis / complications
  • Gastritis / immunology*
  • Gastritis / microbiology
  • Gastritis / pathology*
  • Helicobacter / classification
  • Helicobacter / pathogenicity*
  • Helicobacter Infections / complications*
  • Helicobacter Infections / immunology
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter hepaticus / pathogenicity*
  • Helicobacter pylori / pathogenicity*
  • Mice
  • Mice, Inbred C57BL
  • Severity of Illness Index
  • Stomach / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Cytokines