Helicobacter pylori Induces an Antimicrobial Response in Rhesus Macaques in a cag Pathogenicity Island-Dependent Manner

Michael J. Hornsby, Jennifer L. Huff, Robert J. Kays, Don R. Canfield, Charles L Bevins, Jay V Solnick

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

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 (J166Δcag 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 J166Δcag PAI. Histopathology demonstrated that inflammation and expansion of the lamina propria were attenuated in animals infected with J166Δcag 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 J166Δcag 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.

Original languageEnglish (US)
Pages (from-to)1049-1057
Number of pages9
JournalGastroenterology
Volume134
Issue number4
DOIs
StatePublished - Apr 2008

ASJC Scopus subject areas

  • Gastroenterology

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