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

Abstract

Simple Summary Toxoplasma gondii is a common parasite that infects the intestines of a wide range of animals, including humans, yet we still do not fully understand how the intestine responds to this invader at the level of proteins, i.e., the actual molecules undertaking most intracellular functions. In this study, we infected mice with this parasite and measured thousands of proteins in their intestinal tissues with a high-sensitivity technology. The results show that the parasite causes extensive protein landscape reorganization in the gut. The host activates numerous proteins involved in inflammation and anti-parasite defense while reducing proteins that maintain normal digestion and the protective gut barrier. More importantly, we discovered that the host strategically boosts its cellular machinery for generating and recycling proteins, likely to meet the high demand for defensive proteins. These findings point to a trade-off: the gut prioritizes anti-infection by directing resources away from routine functions, possibly contributing to tissue damage during the acute infection. This study plots a comprehensive protein map that offers new insights into gut defense mechanisms and may help guide future efforts to develop therapies that modulate the host response rather than targeting the parasite directly.