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

Helminth infections are among the most prevalent neglected tropical diseases, causing an enormous impact in health and the socioeconomic status of developing countries. The study host-parasite interactions constitute a promising approach for developing new tools to control these infections. Echinostoma caproni 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.

Male ICR mice were infected with E. caproni. 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.

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.

The primary E. caproni 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.