Susceptibility of mice to primary Echinostoma caproni infections is associated with metabolic and structural changes

Background: is an extensively used model to study host-parasite interactions with emphasis on the factors determining the course of the infections. Herein, we study how infection-induced changes influence host susceptibility and pathology by a proteomic approach. Methods: . Ileal epithelial cells were isolated 4 weeks post-infection, and proteins were extracted for LC-MS/MS analysis using DDA and SWATH. Differential expression was quantified and analyzed with bioinformatics tools. Results: The infection induced strong upregulation of proteins involved in mitochondrial oxidative phosphorylation, purine metabolism, and exopeptidases activating the renin-angiotensin system, fostering oxidative stress and inflammation. Downregulated proteins included those linked to fatty acid β-oxidation, nucleotide binding, vesicular trafficking, and tight junction maintenance, indicating impaired epithelial homeostasis. Antimicrobial peptides were overexpressed, while eosinophil- and neutrophil-derived effectors were reduced, suggesting a skewed Th1-biased profile. Conclusion: infection in mice triggers profound metabolic and immunological reprogramming, characterized by mitochondrial dysfunction, oxidative stress, and epithelial barrier disruption. These alterations, together with an unbalanced antimicrobial and immune response, shape a pro-inflammatory environment that favors chronic infection. Our findings provide novel insights into the molecular basis of host susceptibility to intestinal helminths and may serve for future therapeutic or preventive strategies.