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Early colonic damage and invasion of Campylobacter jejuni in experimentally challenged infant Macaca mulatta
R G Russell1, M O'Donnoghue, D C Blake
1Department of Pathology, School of Medicine, University of Maryland, Baltimore.
Abstract:
Experimental challenge studies with Campylobacter jejuni were conducted in 3.5-month-old infant Macaca mulatta. One infant monkey (92-1) was challenged with 2.7 x 10(10) cfu of strain 78-37. A second infant was infected intentionally by natural transmission. The infants developed diarrhea 32 h after challenge of infant 92-1. Electron microscopic observations indicate that cell invasion is the primary mechanism of colon damage and diarrheal disease caused by C. jejuni. Intracellular C. jejuni were located in membrane-bound vacuoles and were free in the cytoplasm. Damaged epithelial cells exhibited premature apoptosis and were exfoliated into the lumen of the colon. C. jejuni were also located extracellularly in the mucosa and submucosa. Some cells had dilated endoplasmic reticulum, indicating possible alteration in ion and water transport.
Insights
Campylobacter jejuni causes infant monkey diarrhea by invading colon cells, leading to damage and apoptosis. This study reveals cell invasion as the primary mechanism behind the diarrheal disease.
Area of Science:
- Microbiology
- Pathology
- Primate Models
Background:
- Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide.
- Infant susceptibility to enteric pathogens requires further investigation.
Purpose of the Study:
- To investigate the pathogenesis of Campylobacter jejuni infection in infant non-human primates.
- To elucidate the cellular mechanisms underlying C. jejuni-induced diarrheal disease.
Main Methods:
- Experimental challenge studies using infant Macaca mulatta.
- Infection with a specific strain of Campylobacter jejuni (78-37).
- Electron microscopy to examine colon tissue and bacterial interactions.
Main Results:
- Infant monkeys developed diarrhea 32 hours post-challenge.
- Electron microscopy confirmed C. jejuni invasion into colon epithelial cells.
- Intracellular bacteria were observed within vacuoles and free in the cytoplasm.
- Epithelial cell damage included apoptosis and exfoliation.
- Extracellular bacteria were found in the mucosa and submucosa.
- Dilated endoplasmic reticulum suggested altered ion and water transport.
Conclusions:
- Cell invasion is the primary mechanism of colon damage in C. jejuni infection.
- C. jejuni induces apoptosis and disrupts epithelial barrier function.
- The primate model provides insights into C. jejuni pathogenesis and potential therapeutic targets.