Reduced activation of inflammatory responses in host cells by mouse-adapted Helicobacter pylori isolates

Abstract

Summary Helicobacter pylori strains that harbour the Cag pathogenicity island (Cag PAI) induce interleukin (IL)‐8 secretion in gastric epithelial cells, via the activation of NF‐κB, and are associated with severe inflammation in humans. To investigate the influence of Cag PAI‐mediated inflammatory responses on H. pylori adaptation to mice, a selection of H. pylori clinical isolates (n= 12) was cag PAI genotyped and tested in co‐culture assays with AGS gastric epithelial cells, and in mouse colonization studies. Six isolates were shown to harbour a complete cag PAI and to induce NF‐κB activation and IL‐8 secretion in AGS cells. Of the eight isolates that spontaneously colonized mice, six had a cag PAI– genotype and did not induce pro‐inflammatory responses in these cells. Mouse‐to‐mouse passage of the two cag PAI+‐colonizing strains yielded host‐adapted variants that infected mice with bacterial loads 100‐fold higher than those of the respective parental strains (P= 0.001). These mouse‐adapted variants were affected in their capacity to induce pro‐inflammatory responses in host cells, yet no changes in cag PAI gene content were detected between the strains by DNA microarray analysis. This work provides evidence for in vivo selection of H. pylori bacteria with a reduced capacity to induce inflammatory responses and suggests that such bacteria are better adapted to colonize mice.

Nucleotide Oligomerization Domain 1 Enhances IFN-γ Signaling in Gastric Epithelial Cells during Helicobacter pylori Infection and Exacerbates Disease Severity

“…pylori strains 251 (36) and G27 (37) and isogenic 251 ΔcagPAI (38), G27 ΔcagA, and G27 ΔcagM (this study) mutants were constructed by natural transformation as described previously (39). Bacteria were cultured in microaerobic conditions on blood agar medium (40).…”

Helicobacter pyloriInduces MAPK Phosphorylation and AP-1 Activation via a NOD1-Dependent Mechanism

“…pylori strains 251 (36) and G27 (37) are clinical isolates and isogenic 251 ⌬cagPAI was constructed by natural transformation (38,90) and G27 ⌬cagA and ⌬cagM mutants were constructed as described previously (10,39). Bacteria were routinely cultured on blood agar medium, supplemented or not with 10 g/ml kanamycin, under microaerophilic conditions (40).…”

Indistinguishable cellular changes in gastric mucosa between Helicobacter pylori infected asymptomatic tribal and duodenal ulcer patients

“…Thus, the bacterial genotype, host genetic factors and environmental factors, all may have important influence in the disease outcome of H pylori infected people. At least two reports of decreased virulence apparently being selected in vivo have appeared: one during human infection [23] and another during adaptation of human strains to mice [24] . Lack of virulence might also reflect features of the host.…”