Helicobacter pylori induces an antimicrobial response in rhesus macaques in a Cag Pathogenicity Island-Dependent Manner
| Autor: | Charles L. Bevins, Robert J. Kays, Jennifer L. Huff, Don R. Canfield, Michael Hornsby, Jay V. Solnick |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
beta-Defensins Biopsy Molecular Sequence Data Colony Count Microbial Receptors Cell Surface Siderocalin Article Endoscopy Gastrointestinal Antigen Bacterial Proteins Gastric mucosa medicine Animals Humans Specific-pathogen-free Antigens Bacterial Hepatology biology Flavoproteins Helicobacter pylori Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Proteins Calcium-Binding Proteins Gastroenterology NADPH Oxidases biology.organism_classification Molecular biology Pathogenicity island Dual Oxidases Immunohistochemistry Macaca mulatta Elafin DNA-Binding Proteins Disease Models Animal RNA Bacterial medicine.anatomical_structure Beta defensin Gene Expression Regulation Gastric Mucosa Gastritis Immunology Female |
| Popis: | Background & Aims: We used the rhesus macaque model to study the effects of the cag pathogenicity island ( cag PAI) on the H pylori host-pathogen interaction. Methods: H pylori– specific pathogen-free (SPF) monkeys were experimentally challenged with wild-type (WT) H pylori strain J166 (J166WT, n=4) or its cag PAI isogenic knockout (J166Δ cag PAI, n=4). Animals underwent endoscopy before and 1, 4, 8, and 13 weeks after challenge. Gastric biopsies were collected for quantitative culture, histopathology, and host gene expression analysis. Results: Quantitative cultures showed that all experimentally challenged animals were infected with J166WT or its isogenic J166Δ cag PAI. Histopathology demonstrated that inflammation and expansion of the lamina propria were attenuated in animals infected with J166Δ cag PAI compared with J166WT. Microarray analysis showed that of the 119 up-regulated genes in the J166WT-infected animals, several encode innate antimicrobial effector proteins, including elafin, siderocalin, DMBT1, DUOX2, and several novel paralogues of human-β defensin-2. Quantitative RT-PCR confirmed that high-level induction of each of these genes depended on the presence of the cag PAI. Immunohistochemistry confirmed increased human-β defensin-2 epithelial cell staining in animals challenged with J166WT compared with either J166Δ cag PAI-challenged or uninfected control animals. Conclusions: We propose that one function of the cag PAI is to induce an antimicrobial host response that may serve to increase the competitive advantage of H pylori in the gastric niche and could even provide a protective benefit to the host. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|