INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Jia-Hui Cheng,Xiang Xu,Ying-Biao Li,Xu-Dong Zhao,Fumie Aosai,Su-Yun Shi,Cheng-Hua Jin,Jing-Shu Piao,Juan Ma,Hu-Nan Piao,Xue-Jun Jin,Lian-Xun Piao
Toxoplasma gondii ( T. gondii ) is a known neurotropic protozoan that remains in the central nervous system and induces neuropsychiatric diseases in intermediate hosts. Arctigenin (AG) is one of the major bioactive lignans of the fruit Arctium lappa L. and has a broad spectrum of pharmacological activities such as neuroprotective, anti-inflammatory and anti- T. gondii effects. However, the effect of AG against depressive behaviors observed in T. gondii -infected hosts has not yet been clarified. In the present study, we analyzed the effects of AG against T. gondii -induced depressive behaviors in intermediate hosts using a microglia cell line (BV2 cells) and brain tissues of BALB/c mice during the acute phase of infection with the RH strain of T. gondii . AG attenuated microglial activation and neuroinflammation via the Toll-like receptor/nuclear factor-kappa B (NF-κB) and tumor necrosis factor receptor 1/NF-κB signaling pathways, followed by up-regulating the dopamine and 5-hydroxytryptamine levels and inhibiting the depression-like behaviors of hosts. AG also significantly decreased the T. gondii burden in mouse brain tissues. In conclusion, we elucidated the effects and underlying molecular mechanisms of AG against depressive behaviors induced by T. gondii infection.
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DOI
PubMed
高影响因子
Parasites & Vectors
·
2025
·Vol. 18
·期 1
·1-15
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IF 3.5
Geng Xiao-Ling,Li Jing-Yu,Xu Huan-Yu,Wu Jiang-Ping,Tao De-Liang,Chen Jin-Ming,Fan Ying-Ying,Yang Xin,Song Jun-Ke,Zhao Guang-Hui
Background The pathogenicity of Toxoplasma gondii is closely associated with its intracellular lytic cycle in host cells. Currently, the mechanisms by which T. gondii completes the lytic cycle remain unclear. The proline metabolism has been reported to be crucial for intracellular growth of pathogens by providing energy and nutrients. However, it remains unclear whether the intracellular growth and pathogenicity of T. gondii are related to proline metabolism.Methods The gene-edited strains of proline dehydrogenase (Tgprodh) were constructed by using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR–Cas9) technology. The effects of the Tgprodh gene on the growth in vitro and pathogenicity in vivo of the tachyzoites for T. gondii were studied through proliferation, plaque, invasion, egress and virulence assays. The effects of the Tgprodh gene on mitochondrial function were studied by using reactive oxygen species (ROS), mitochondrial membrane potential (∆Ψm), adenosine triphosphate (ATP) assay kits, mitochondrial DNA (mtDNA) copy numbers, transmission electron microscopy (TEM) analysis, and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The effects of the Tgprodh gene on proline metabolism were studied by using l-proline (L-Pro), l-glutamic acid (L-Glu), l-glutamine (L-Gln) assay kits, and RT-qPCR.Results TgPRODH, the first rate-limiting enzyme in proline metabolism, was identified to be encoded by T. gondii and localized in the cytoplasm of T. gondii. Deletion of the Tgprodh gene resulted in significant growth inhibition in vitro and reduced pathogenicity in vivo of T. gondii. Further study found that deletion of the Tgprodh gene caused damage to the mitochondrial morphology, decreased membrane potential, mtDNA copy numbers, and the production of ATP and ROS. The expression of genes for maintaining mitochondrial integrity was downregulated in the Tgprodh-knockout strain of T. gondii, while complementation of the Tgprodh gene restored these defects in this parasite. Meantime, the deletion of the Tgprodh gene resulted in the accumulation of proline, reduced the contents of glutamate and glutamine, and affected the expression of genes related to proline catabolism in T. gondii.Conclusion sThe present study found the significance of the Tgprodh gene for the intracellular growth and pathogenicity of T. gondii through regulating mitochondrial function and the proline metabolism and provided a novel insight to reveal intracellular survival strategies of T. gondii.Graphical
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Jing-Mei Lu,Xiang Xu,Fumie Aosai,Ming-Yue Zhang,Lu-Lu Zhou,Lian-Xun Piao
Toxoplasma gondii ( T. gondii )-derived heat shock protein 70 ( T.g. HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g. HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A 2 (cPLA 2 ) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii ) on allergic liver injury using T.g. HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii -induced allergic acute liver injury. The results showed that ARC suppressed the T.g. HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g. HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA 2 , PAF, and interferon-γ. This result suggested that ARC ameliorates T.g. HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g. HSP70-induced allergic liver injury.
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PubMed
高影响因子
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