Proinflammatory pathways contribute to the pathogenesis of Clostridioides difficile infection in a murine model using...

Area of Science:

• Microbiology
• Genomics
• Immunology

Background:

• Clostridioides difficile infection (CDI) is a major cause of hospital-acquired diarrhea with limited treatment options.
• Recurrence and treatment failure are common in CDI, necessitating further research into disease mechanisms.

Purpose of the Study:

• To investigate differential gene expression in symptomatic versus asymptomatic mice post-C. difficile infection.
• To analyze spatial gene expression patterns within intestinal mucosal layers.
• To identify key molecular pathways involved in CDI pathogenesis.

Main Methods:

• Spatial transcriptomics analysis of formalin-fixed paraffin-embedded (FFPE) intestinal sections from C. difficile-infected mice.
• Utilized the NanoString platform for differential gene expression analysis in the caecum and colon.
• Compared gene expression profiles between superficial and deep layers of the intestinal mucosa.

Main Results:

• The IL-17 pathway, including Lcn2, Cxcl2, and S100a8 genes, was significantly upregulated in symptomatic mice.
• Activated IL-17 signaling led to downstream activation of NF-κB and MAPK pathways.
• Significant alterations in gene expression were observed between superficial and deep intestinal mucosal layers, indicating layer-specific responses.

Conclusions:

• Spatial transcriptomics reveals distinct gene expression patterns in CDI, correlating with disease severity.
• The IL-17 pathway plays a crucial role in the host response to C. difficile infection.
• Layer-specific gene expression in the enteric mucosa contributes to the clinical manifestations of CDI.