Campylobacter concisus pathotypes induce distinct global responses in intestinal epithelial cells

Area of Science:

• Microbiology
• Cell Biology
• Immunology

Background:

• The opportunistic pathogen Campylobacter concisus interactions with the host intestinal epithelium are not well understood.
• Understanding these interactions is crucial for identifying mechanisms of C. concisus-associated diseases.

Purpose of the Study:

• To characterize the distinct intestinal epithelial responses to different C. concisus strains.
• To investigate the role of the C. concisus zonula occludens toxin (ZOT) in modulating epithelial responses.

Main Methods:

• RNA sequencing (RNAseq) was used to analyze gene expression changes in Caco-2 cells exposed to C. concisus strains and purified ZOT.
• Quantitative polymerase chain reaction (qPCR) arrays were employed to validate RNAseq findings.
• ZOT was expressed and purified for direct experimental analysis.

Main Results:

• Distinct gene expression profiles were observed in response to different C. concisus strains, with the toxigenic strain eliciting a stronger response.
• Key cellular processes including epithelial-to-mesenchymal transition, cytoskeletal remodeling, tight junction regulation, inflammation, and autophagy were differentially regulated.
• ZOT was found to upregulate PAR2, TLR3, pro-inflammatory cytokines (IL6, IL8), CXCL16, and caspase-7, impacting tight junctions and cytoskeletal dynamics.

Conclusions:

• C. concisus strains induce specific and varied epithelial responses, influenced by virulence factors like ZOT.
• Nucleic acid sensing via pattern recognition receptors (TLR3, IFI16) appears important for epithelial recognition of C. concisus.
• C. concisus ZOT contributes to host-pathogen interactions by modulating epithelial cell functions and inflammatory signaling.