Study of Helicobacter pylori infection on lung using an animal model

Microb Pathog. 2018 Oct:123:410-418. doi: 10.1016/j.micpath.2018.07.038. Epub 2018 Jul 26.


Helicobacter pylori infection has been reported to be associated with extra-digestive disorders such as respiratory diseases; however, the impact of H. pylori on lung is incompletely understood. Inflammatory response is mediated by the release of cytokines, interferon, and enzymes such as metalloproteinases (MMPs). This may contribute to collagen accumulation during the early phase of infection. MMP expression is an important factor for the proliferation and infiltration of lung cells in the process of fibrosis formation. The aim of this work was to study the impact of the infection with H. pylori on lung using a mouse model. We looked for histological lesions of lung infected with the microorganism as well as the expression of inflammatory and of endothelial dysfunction markers. C57BL/6 wild type (WT) mice were infected by orotracheal instillation with 20 μl of 1 × 108H. pylori reference strain suspension once per day for 3 days. Animals infected and controls were sacrificed at 3, 7, 14, 21 and 30 days. The lung from mice were stained with Hematoxylin-Eosin (H-E), Masson's Trichromic and Periodic Acid Schifft (PAS) for histological study. Also, lipid hydroperoxides and enzime catalase (CAT) activity were determined. Expression level of multiple markers implicated in inflammation (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10; metalloproteinase MMP-9) and markers of endothelial dysfunction (I-CAM and V-CAM) was determined from lung tissues mRNA using RT-PCR. Results showed that H. pylori induced morphological changes in the lung tissue with recruitment of inflammatory cells and lung parenchymal cell degradation. The mRNA of IL-1β and TNF-α; MMP-9, I-CAM and V-CAM increased at 3-7 days infections. Also, iNOS, IL-8 and Phosphocholine cytidyltransferase (CCT) increased with lung injury. Anti-inflammatory interleukin as: IL-4, and IL-10 increased at 7 and 14 days post infection respectively. The results obtained suggest that the pathogenic mechanism of H. pylori on lung could be strongly associated with lung injury as indicate the expression increased of inflammatory mediators and markers of endothelial dysfunction.

MeSH terms

  • Animals
  • Biomarkers
  • Bronchoalveolar Lavage
  • Catalase / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • DNA, Bacterial / analysis
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Endothelial Cells / microbiology
  • Gene Expression
  • Helicobacter Infections / pathology*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / pathogenicity*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Lung / microbiology*
  • Lung / pathology*
  • Lung Injury / metabolism
  • Lung Injury / microbiology*
  • Lung Injury / pathology*
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type II / metabolism
  • RNA, Ribosomal, 16S / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Biomarkers
  • Cytokines
  • DNA, Bacterial
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • RNA, Ribosomal, 16S
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Catalase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Matrix Metalloproteinase 9