Persistent Salmonella enterica Serovar Typhimurium Infection Induces Protease Expression During Intestinal Fibrosis

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Intestinal fibrosis, a complication of Crohn's disease, involves fibroblast accumulation and scar tissue formation.
• The precise initiating mechanisms and interplay of factors like cytokines and proteases in intestinal fibrosis are not fully understood.

Purpose of the Study:

• To investigate the role of proteases and protease inhibitors in Salmonella-induced intestinal fibrosis.
• To establish a murine model for studying intestinal fibrosis.

Main Methods:

• Induction of intestinal fibrosis in mice via chronic Salmonella enterica serovar Typhimurium infection.
• Murine protease-specific CLIP-CHIP microarray analysis to identify regulated proteases and inhibitors.
• Validation using quantitative real-time PCR and immunohistochemistry in mouse and human tissues.
• In vitro infection models to assess direct bacterial effects on protease expression.

Main Results:

• Chronic Salmonella infection successfully induced severe intestinal fibrosis in mice, mirroring human pathology.
• Microarray analysis identified significant dysregulation of 56 proteases and 40 protease inhibitors in fibrotic tissue.
• Quantitative PCR confirmed regulation of 22 proteases, with specific staining patterns observed in mouse and human fibrotic tissues.
• Salmonella infection directly increased protease expression in macrophages and epithelial cells, but not fibroblasts, in vitro.

Conclusions:

• Chronic Salmonella infection modulates protease and protease inhibitor expression during intestinal fibrosis.
• The Salmonella-induced fibrosis model is suitable for further research into the role of proteases in intestinal fibrotic diseases.