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 journalArticle

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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

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Genomic Islands
Macaca mulatta
Helicobacter pylori
Pylorus
Defensins
Stomach
Elafin
Host-Pathogen Interactions
Specific Pathogen-Free Organisms
Microarray Analysis
Endoscopy
Genes
Haplorhini
Mucous Membrane
Epithelial Cells
Immunohistochemistry
Staining and Labeling
Inflammation
Biopsy
Gene Expression

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Helicobacter pylori Induces an Antimicrobial Response in Rhesus Macaques in a cag Pathogenicity Island-Dependent Manner. / Hornsby, Michael J.; Huff, Jennifer L.; Kays, Robert J.; Canfield, Don R.; Bevins, Charles L; Solnick, Jay V.

In: Gastroenterology, Vol. 134, No. 4, 04.2008, p. 1049-1057.

Research output: Contribution to journalArticle

Hornsby, Michael J. ; Huff, Jennifer L. ; Kays, Robert J. ; Canfield, Don R. ; Bevins, Charles L ; Solnick, Jay V. / Helicobacter pylori Induces an Antimicrobial Response in Rhesus Macaques in a cag Pathogenicity Island-Dependent Manner. In: Gastroenterology. 2008 ; Vol. 134, No. 4. pp. 1049-1057.
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