Parasites & vectors · 2025
Toxoplasma gondii-induced ferroptosis contributes to acute lung injury in mice.
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Yuan Xiaodan, Liu Zhenzhen, Ma Yeting, Liu Feixue, Bao Penglin, Du Boya, Zhang Xu, Gong Pengtao, Zhang Nan, Li Jianhua, Li Xin, Wang Xiaocen
Аннотация
BACKGROUND: Toxoplasma gondii (T. gondii) is an important apicomplexan parasite that causes zoonotic toxoplasmosis in humans and animals. Acute T. gondii infection leads to systemic immunopathology that may manifest as lung injury or pulmonary embolism. Ferroptosis is an iron-dependent regulated cell death driven by lethal lipid hydroperoxide accumulation. Emerging evidence implicates ferroptosis in infection-related tissue damage; however, the role of ferroptosis in T. gondii-induced lung injury remains to be explored.
METHODS: Mice were infected with T. gondii to establish a lung injury model. The body weight changes, survival rate, inflammatory cytokines, lung histopathology, and parasite burden were assessed. The key ferroptosis-related indicators involved in antioxidant, iron metabolism, and lipid metabolism pathways were analyzed in lung tissues using techniques such as transmission electron microscopy, western blotting, and immunohistochemistry. Deferiprone (DFP), an oral iron chelator that can inhibit ferroptosis, was used to investigate the potential role of ferroptosis in T. gondii lung injury.
RESULTS: T. gondii infection induced lung injury in mice with thickening of alveolar septa and hemorrhage in alveolar spaces, accompanied by iron deposition. Crucially, T. gondii triggered ferroptosis in lung tissues of mice, evidenced by MDA elevation, GSH depletion, total iron and Fe2+ overload, and mitochondrial cristae loss. Furthermore, iron metabolism pathways were disordered while antioxidant pathways were suppressed. DFP treatment reversed ferroptosis alterations, decreased inflammatory cytokines, attenuated pathological changes, reduced T. gondii burden, and prolonged survival of the infected mice.
CONCLUSIONS: Our findings revealed that T. gondii infection triggered ferroptosis by compromising dysregulated iron metabolism and antioxidant defenses, playing a key role in T. gondii-induced lung injury. DFP exhibited a promising therapy effect for toxoplasmosis.
METHODS: Mice were infected with T. gondii to establish a lung injury model. The body weight changes, survival rate, inflammatory cytokines, lung histopathology, and parasite burden were assessed. The key ferroptosis-related indicators involved in antioxidant, iron metabolism, and lipid metabolism pathways were analyzed in lung tissues using techniques such as transmission electron microscopy, western blotting, and immunohistochemistry. Deferiprone (DFP), an oral iron chelator that can inhibit ferroptosis, was used to investigate the potential role of ferroptosis in T. gondii lung injury.
RESULTS: T. gondii infection induced lung injury in mice with thickening of alveolar septa and hemorrhage in alveolar spaces, accompanied by iron deposition. Crucially, T. gondii triggered ferroptosis in lung tissues of mice, evidenced by MDA elevation, GSH depletion, total iron and Fe2+ overload, and mitochondrial cristae loss. Furthermore, iron metabolism pathways were disordered while antioxidant pathways were suppressed. DFP treatment reversed ferroptosis alterations, decreased inflammatory cytokines, attenuated pathological changes, reduced T. gondii burden, and prolonged survival of the infected mice.
CONCLUSIONS: Our findings revealed that T. gondii infection triggered ferroptosis by compromising dysregulated iron metabolism and antioxidant defenses, playing a key role in T. gondii-induced lung injury. DFP exhibited a promising therapy effect for toxoplasmosis.