Abstract

Helicobacter (H.) heilmannii sensu stricto (s.s.) is a zoonotic bacterium that naturally colonizes the stomach of dogs and cats. In humans, this microorganism has been associated with gastritis, peptic ulcer disease and mucosa associated lymphoid tissue (MALT) lymphoma. Little information is available about the pathogenesis of H. heilmannii s.s. infections in humans and it is unknown whether differences in virulence exist within this species. Therefore, a Mongolian gerbil model was used to study bacterium-host interactions of 9 H. heilmannii s.s. strains. The colonization ability of the strains, the intensity of gastritis and gene expression of various inflammatory cytokines in the stomach were determined at 9 weeks after experimental infection. The induction of an antrum-dominant chronic active gastritis with formation of lymphocytic aggregates was shown for 7 strains. High-level antral colonization was seen for 4 strains, while colonization of 4 other strains was more restricted and one strain was not detected in the stomach at 9 weeks post infection. All strains inducing a chronic active gastritis caused an up-regulation of the pro-inflammatory cytokine IL-1β in the antrum. A reduced antral expression of H+/K+ ATPase was seen in the stomach after infection with 3 highly colonizing strains and 2 highly colonizing strains caused an increased gastrin expression in the fundus. In none of the H. heilmannii s.s.-infected groups, IFN-γ expression was up-regulated. This study demonstrates diversity in bacterium-host interactions within the species H. heilmannii s.s. and that the pathogenesis of gastric infections with this microorganism is not identical to that of an H. pylori infection.

Highlights

  • Helicobacter (H.) pylori is the most prevalent Helicobacter species colonizing the gastric mucosa of humans and has been associated with gastritis, peptic ulcer disease and gastric cancer [1,2,3]

  • Inflammation in the stomach of gerbils infected with H. heilmannii s.s. strains ASB1, ASB2, ASB3, ASB6, ASB11, ASB13 and ASB14 was marked by a chronic active gastritis with formation of lymphocytic aggregates in the lamina propria and submucosa of the antrum of the stomach (Figure 1b)

  • At 9 weeks post inoculation, a chronic active gastritis in the antrum of the stomach was observed in gerbils experimentally infected with 7 out of 9 H. heilmannii s.s. strains tested in this study (ASB1, ASB2, ASB3, ASB6, ASB11, ASB13 and ASB14)

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Summary

Introduction

Helicobacter (H.) pylori is the most prevalent Helicobacter species colonizing the gastric mucosa of humans and has been associated with gastritis, peptic ulcer disease and gastric cancer [1,2,3]. NHPH represents a group of closely related but distinct bacterial species, mainly found in different animal species, such as H. felis, H. salomonis, H. bizzozeronii, H. heilmannii sensu stricto (s.s.), H. cynogastricus and H. baculiformis in cats and dogs and H. suis in pigs [5,7,10,11,12,13,14,15]. These microorganisms are characterized by their extremely fastidious nature, which so far has resulted in a limited number of in vitro isolates available worldwide.

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