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Updated: Jul 8, 2026
3-D Imaging and Analysis of Neurons Infected In Vivo with Toxoplasma gondii
Published on: December 9, 2014
Microglial PTP1B promotes synaptic pathology and cognitive deficits in chronic Toxoplasma gondii infection
Daxiang Xu1, Cheng He2, Huiling Lv2
1Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China; National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China; Key Laboratory of Parasite and Vector Biology, National Health Commission of the People's Republic of China, Shanghai, China; World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.
Abstract:
Chronic infection with the neurotropic pathogen Toxoplasma gondii has been epidemiologically associated with a risk of neurodegeneration; however, the mechanisms driving infection-associated cognitive decline remain unclear. We investigated the role of microglial protein-tyrosine phosphatase 1B (PTP1B) as a potential driver of neuropathology in chronic toxoplasmosis. Using a murine model, we demonstrate that PTP1B expression is elevated in the hippocampus following infection. Global genetic ablation or pharmacological inhibition of PTP1B rescued infection-induced cognitive deficits and mitigated neuroinflammation. Crucially, microglia-specific deletion of Ptp1b prevented synaptic loss and cognitive impairment. Mechanistically, we show that microglial PTP1B potentiates the nuclear factor-kappa B (NF-κB) pathway, promoting complement component 1q (C1q)-mediated synaptic tagging and subsequent neuronal structural damage. Validating the clinical relevance of these findings, we observed significantly elevated PTP1B levels in peripheral blood mononuclear cells from T. gondii-seropositive individuals, which correlated with inflammatory markers. Overall, our findings identify microglial PTP1B as a pivotal mediator of T. gondii-associated neurodegeneration.
Insights
Chronic Toxoplasma gondii infection elevates microglial protein-tyrosine phosphatase 1B (PTP1B), driving cognitive decline and neuroinflammation. Inhibiting PTP1B in mice prevented synaptic loss and cognitive impairment, suggesting PTP1B as a therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Chronic Toxoplasma gondii infection is linked to neurodegeneration and cognitive decline.
- The precise mechanisms underlying infection-associated cognitive impairment are not fully understood.
Purpose of the Study:
- To investigate the role of microglial protein-tyrosine phosphatase 1B (PTP1B) in Toxoplasma gondii-associated neuropathology.
- To explore PTP1B as a potential therapeutic target for mitigating cognitive deficits.
Main Methods:
- Utilized a murine model of chronic toxoplasmosis.
- Assessed PTP1B expression in the hippocampus post-infection.
- Employed global genetic ablation and pharmacological inhibition of PTP1B.
- Conducted microglia-specific Ptp1b deletion studies.
- Analyzed peripheral blood mononuclear cells from T. gondii-seropositive individuals.
Main Results:
- PTP1B expression was significantly elevated in the hippocampus after infection.
- Global PTP1B inhibition or ablation reversed cognitive deficits and reduced neuroinflammation.
- Microglia-specific Ptp1b deletion prevented synaptic loss and cognitive impairment.
- Mechanistically, microglial PTP1B was shown to enhance the NF-κB pathway, leading to C1q-mediated synaptic damage.
- Elevated PTP1B levels correlated with inflammatory markers in infected individuals.
Conclusions:
- Microglial PTP1B is a key mediator of neurodegeneration and cognitive decline in chronic toxoplasmosis.
- Targeting microglial PTP1B offers a promising therapeutic strategy for neurodegenerative conditions associated with T. gondii infection.
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