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Preventive effect of pidotimod on reactivated toxoplasmosis in mice

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Abstract

As one of food-borne parasitic diseases, toxoplasmosis entails the risk of developing reactivation in immunocompromised patients. The synthetic dipeptide pidotimod is a potent immunostimulating agent that improves the immunodefenses in immunodepression. To investigate the efficacy of pidotimod as a preventive treatment, we used a murine model of reactivated toxoplasmosis with cyclophosphamide (CY)-induced immunosuppression. Pidotimod administration significantly restored the body weight and spleen organ index, increased survival time (from 70 to 90 %), and decreased the parasitemia (from 80 to 35 %) of CY-induced mice with reactivated toxoplasmosis. Cytokine profiles and CD4+ T cells subpopulation analyses by Cytometric Bead Array and flow cytometry demonstrated that pidotimod treatment resulted in a significant upregulation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) and Th1 cells (from 3.73 ± 0.39 to 5.88 ± 0.46 %) after CY induction in infected mice. Additionally, histological findings and parasite DNA quantification revealed that mice administered with pidotimod had a remarkable reduction of parasite burden (two-log) and amelioration of histopathology in the brains. The in vitro studies showed that pidotimod significantly restored concanavalin A-induced splenocyte proliferation and pro-inflammatory cytokines in the supernatants of splenocyte culture. It could be concluded that the administration of pidotimod in immunocompromised mice significantly increases the Th1-biased immune response, prolongs survival time, and ameliorates the load of parasites in the blood. This is the first report of the preventive effect of pidotimod on reactivated toxoplasmosis.

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Acknowledgments

This work was funded by the National Basic Research Program of China (973 Program, Grant No. 2010CB530001) and Natural Science Foundation of China (Grant Nos. 81171605 and 81271864). Our thanks to Prof. Geoff Hide at University of Salford, Salford, UK for his kind language polishing and comments.

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Authors and Affiliations

  1. The Key Laboratories of Parasitology and Zoonoses Anhui and Department of Parasitology, Anhui Medical University, Hefei, 230032, People’s Republic of China

    Xing-Xing Huo, Lin Wang, He Chen, Qing-Li Luo, Yu Fu, Hua Wang, Jian Du, Yi-Hong Cai & Ji-Long Shen

  2. Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China

    Xing-Xing Huo, He Chen & Yuan-Hong Xu

  3. Clinical Laboratory Center, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230031, People’s Republic of China

    Xing-Xing Huo

  4. Anhui Provincial Hospital, Hefei, 230001, People’s Republic of China

    Zhao-Wu Chen, Xiu-Cai Xu, Ai-Mei Zhang, Xiao-Rong Song & Yu Fu

  5. State Key Laboratory of Biocontrol, School of Life Sciences, Key Laboratory of Tropical Diseases Control, The Ministry of Education, and The Department of Parasitology, Zhongshan Medical College, Sun Yat-Sen (Zhongshan) University, Guangzhou, 510275, People’s Republic of China

    Zhao-Rong Lun & Fang-Li Lu

  6. Department of Pathogen Biology, Nanjing Medical University, Nanjing, 210029, People’s Republic of China

    Yong Wang

  7. Institute of Zoonoses and Parasitology, Anhui Medical University, No. 81, Meishan Road, Hefei, 230032, People’s Republic of China

    Ji-Long Shen

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  1. Xing-Xing Huo
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  16. Yong Wang
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  17. Ji-Long Shen
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Correspondence to Ji-Long Shen.

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Xing-Xing Huo and Lin Wang contributed equally to this work.

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Huo, XX., Wang, L., Chen, ZW. et al. Preventive effect of pidotimod on reactivated toxoplasmosis in mice. Parasitol Res 112, 3041–3051 (2013). https://doi.org/10.1007/s00436-013-3488-y

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  • DOI: https://doi.org/10.1007/s00436-013-3488-y

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