Integrated Proteomic Profiling Reveals Dynamic Remodeling of the Intestinal Proteome in Toxoplasma gondii-Infected C57BL/6J Mice

Abstract

The intestinal mucosa is the primary site of Toxoplasma gondii (T. gondii) infection and interaction with the host. While the intestinal responses have been characterized through transcriptomic and histopathological studies, a comprehensive, system-wide analysis of the functional proteome remodeling by acute T. gondii infection is required to elucidate the underlying mechanisms. This study presents a temporal, quantitative proteomic profiling of T. gondii-infected C57BL/6J mouse intestine to define the protein-centric host response. Global analysis reveals profound reprogramming, characterized by upregulated acute-phase reactants and interferon-stimulated effectors and downregulated epithelial barrier and digestive function proteins. Systems-level bioinformatics analysis uncovers a coordinated host strategy of cellular resource reallocation, evidenced by the simultaneous and specific amplification of ribosome biogenesis and proteasomal degradation pathways. Subsequent protein–protein interaction network analysis substantiates this strategic investment in core protein homeostasis infrastructure, identifying the ribosome biogenesis machinery as the topological core of the response interactome. These findings support a model of defense-priority resource reallocation. That is, the host redirects cellular resources to optimize its biosynthetic and catabolic capacity, facilitating a high-output immune response at the potential expense of tissue homeostasis. This work provides an integrated proteomic atlas of the intestinal immunopathology mechanisms during toxoplasmosis and establishes a foundation for future host-directed therapeutic exploration.