Helicobacter pylori induces an antimicrobial response in rhesus Macaques in a cag pathogenicity island-dependent manner

Background & Aims: We used the rhesus macaque model to study the effects of the cag pathogenicity island (cag PAT) 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 PAT isogenic knockout (J166 Delta 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 J166 Delta cag PAT. Histopathology demonstrated that inflammation and expansion of the lamina propria were attenuated in animals infected with J166 Delta cag PAT 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-beta 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-beta defensin-2 epithelial cell staining in animals challenged with J166WT compared with either J166 Delta cag PAI-challenged or uninfected control animals. Conclusions: We propose that one function of the cag PAT 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.