Physical exercise protects against Toxoplasma gondii infection-induced muscle atrophy and microvascular rarefaction

Toxoplasmosis is a leading cause of death from foodborne illness. Its causative agent, Toxoplasma gondii, forms cysts in skeletal muscle, contributing to parasite persistence and transmission. Cases of myositis have been reported in T. gondii-infected immunocompetent individuals, and impaired myogenesis has been demonstrated in mice. Herein we investigated the effects of T. gondii infection on glycolytic tibialis anterior (TA) and oxidative soleus (SOL) muscles in mice, and whether prior physical exercise could prevent infection-induced myopathology. Functional, metabolic, histological, inflammatory and microvascular parameters were analyzed 10 and 40 days post infection (dpi). T. gondii caused greater disruption to TA than to SOL, with increased atrophy and pathology. Expression of muscle atrophy-related genes (Atrogenes), including MURF1 and Atrogin-1, was strongly induced at 10 and normalized by 40 dpi. A fiber-type shift was observed in SOL at 40 dpi. Infected sedentary mice showed reduced grip strength and VO₂, while these effects were prevented by exercise. Exercised-infected mice had lower expression of Murf1, IL-6ra, STAT3, and pro/anti-inflammatory cytokine ratios compared to sedentary-infected controls. Exercise also preserved muscle and brain microvascular flow and prevented leukocyte-endothelium interactions. In conclusion, T. gondii differentially affects glycolytic and oxidative muscles; exercise protects muscle and brain against parasite-related damage.