Helicobacter pylori induces an antimicrobial response in rhesus macaques in a cag pathogenicity island-dependent manner.
OBJECTIVE
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 (J166Deltacag 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 J166Deltacag PAI. Histopathology demonstrated that inflammation and expansion of the lamina propria were attenuated in animals infected with J166Deltacag 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-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 J166Deltacag 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.
Hornsby
Michael J
MJ
Department of Medical Microbiology & Immunology, University of California, Davis, Davis, California, USA.
Huff
Jennifer L
JL
Kays
Robert J
RJ
Canfield
Don R
DR
Bevins
Charles L
CL
Solnick
Jay V
JV
D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D001706:Biopsy; D002135:Calcium-Binding Proteins; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D000074623:Dual Oxidases; D053492:Elafin / Q000235:genetics / Q000378:metabolism; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005786:Gene Expression Regulation; D016480:Helicobacter pylori / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D012329:RNA, Bacterial / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002135:Calcium-Binding Proteins; C106641:DEFB4A protein, human; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D053492:Elafin; D005420:Flavoproteins; D012329:RNA, Bacterial; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D023083:beta-Defensins; C080866:cagA protein, Helicobacter pylori; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human