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Trophoblast apoptosis through polarization of macrophages induced by Chinese Toxoplasma gondii isolates with different virulence in pregnant mice

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Abstract

Toxoplasma gondii is an apicomplexan parasite capable of transplacental transmission to cause spontaneous abortion or significant disease in the surviving neonate. Different from the dominant genotypes of T. gondii strains in European and North American which belong to three distinct clonal lineages, type I, type II, and type III, isolates from China possess the predominant genotype of China 1(ToxoDB#9) with a different virulence. The genotype-associated pathogenesis has been investigated previously. Based on two isolates of T. gondii from Chinese wild cats, a murine model of pregnancy and one transwell system in vitro, here we reported differentially polarized activation of macrophages induced by genotype China 1 strains, TgCtwh3 and TgCtwh6 with different virulence to mice, and its impact on trophoblast apoptosis. The results showed that macrophages were alternatively activated when infected with virulent TgCtwh3 while classically activated when infected with low virulent (cyst-forming) TgCtwh6 both in vitro and in vivo. By the analysis of flow cytometry, the percentage of the Th1 cells in two infection groups decreased significantly, and the Th2 cells from spleen escalated only in the virulent TgCtwh3 group. Interestingly, the high parasite burden was noted in the placenta of TgCtwh3-infected group whereas the inflammatory cells infiltration predominates in the TgCtwh6-infected group. In vivo trophoblast apoptosis in TgCtwh3 group was found to be more obvious when compared with TgCtwh6 although it was present in both. The present observations indicate that polarization of macrophages and modulation of Th subsets induced by the isolates with identical genotype but different virulence could contribute to trophoblast apoptosis through different mechanisms, suggesting a virulence-associated pathogenesis of T. gondii in abnormal pregnant outcome.

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Acknowledgments

This work was funded by the Natural Basic Research Program of China (Grant No. 2010CB530001) and the National Natural Science Foundation of China (Grants No. 81171605 and 81101272). Our thanks are given to Prof. Geoff Hide at Center for Parasitology and Disease, School of Environment and Life Sciences, University of Salford, UK for polishing the language in the manuscript.

Conflict of interest

The authors declare no financial or commercial conflict of interest.

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Authors and Affiliations

  1. Department of Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230022, People’s Republic of China

    Tingting Liu, Qian Zhang, He Chen, Hua Wang, Lanting Kong, Weiwei Wang, Aimei Zhang, Yihong Cai, Min Li, Li Yu, Jian Du, Xuelong Wang, Qingli Luo & Jilong Shen

  2. The Department of Laboratory Diagnosis, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China

    Lili Liu

  3. The Central Laboratory of Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China

    Xiucai Xu & Aimei Zhang

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

    Zhao-Rong Lun

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

    Yong Wang

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  1. Tingting Liu
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  8. Weiwei Wang
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  11. Min Li
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  12. Li Yu
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  14. Xuelong Wang
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  16. Zhao-Rong Lun
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Corresponding authors

Correspondence to Xiucai Xu or Jilong Shen.

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Tingting Liu and Qian Zhang contributed equally to this work.

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Liu, T., Zhang, Q., Liu, L. et al. Trophoblast apoptosis through polarization of macrophages induced by Chinese Toxoplasma gondii isolates with different virulence in pregnant mice. Parasitol Res 112, 3019–3027 (2013). https://doi.org/10.1007/s00436-013-3475-3

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  • DOI: https://doi.org/10.1007/s00436-013-3475-3

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