Integrated Proteomic Profiling Reveals Dynamic Remodeling of the Intestinal Proteome in Toxoplasma gondii-Infected...

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.