The lack of a standardized laboratory animal model that mimics key aspects of human shigellosis remains major obstacle to addressing questions on pathogenesis, screening therapeutics and evaluating vaccines.
We characterize a piglet model for Shigella dysenteriae type 1.
Piglets developed acute diarrhea, anorexia, dehydration and often fatal, with severity depending on age and dose. Bacteria were apparent in the lumen and on surface epithelium throughout the gut initially, but severe mucosal damage and bacterial cellular invasion were most profound in the colon. Detached necrotic colonocytes were present in the lumen, with inflammatory cells outpouring from damaged mucosa. High levels of IL-8 and IL-12, were followed by other proinflammatory cytokines. Elevated TNF-α, IL-1β, IL-6, and IL-10 were detected in feces and in gut segments of infected animals. Bacteria were present inside epithelial cells and within colonic lamina propria. In contrast, an isogenic strain lacking Shiga toxin, induced similar but milder symptoms, with moderate mucosal damage and lower cytokine levels.
We conclude that piglets are highly susceptible to shigellosis providing a useful tool to compare vaccine candidates for immunogenicity, reactogenicity and response to challenge, investigate the role of virulence factors and test the efficacy of microbial agents.