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TatD DNases of African trypanosomes confer resistance to host neutrophil extracellular traps

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Abstract

African trypanosomatid parasites escape host acquired immune responses through periodic antigenic variation of their surface coat. In this study, we describe a mechanism by which the parasites counteract innate immune responses. Two TatD DNases were identified in each of Trypanosoma evansi and Trypanosoma brucei. These DNases are bivalent metal-dependent endonucleases localized in the cytoplasm and flagella of the parasites that can also be secreted by the parasites. These enzymes possess conserved functional domains and have efficient DNA hydrolysis activity. Host neutrophil extracellular traps (NETs) induced by the parasites could be hydrolyzed by native and recombinant TatD DNases. NET disruption was prevented, and the survival rate of parasites was decreased, in the presence of the DNase inhibitor aurintricarboxylic acid. These data suggest that trypanosomes can counteract host innate immune responses by active secretion of TatD DNases to degrade NETs.

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Acknowledgements

We thank Professor Lun Zhaorong from Sun Yat-sen University for providing the parasite of T. brucei and Professor Suo Xun from the China Agricultural University for providing the parasite of T. evansi. This study was supported by the Distinguished Scientist grant from Shenyang Agricultural University and Liaoning Province (8804–880416076), and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-042).

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Authors and Affiliations

  1. Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China

    Kai Zhang, Ning Jiang, Hongyu Chen, Naiwen Zhang, Xiaoyu Sang, Ying Feng, Ran Chen & Qijun Chen

  2. The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, 110866, China

    Kai Zhang, Ning Jiang, Hongyu Chen, Naiwen Zhang, Xiaoyu Sang, Ying Feng, Ran Chen & Qijun Chen

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  1. Kai Zhang
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Correspondence to Qijun Chen.

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Zhang, K., Jiang, N., Chen, H. et al. TatD DNases of African trypanosomes confer resistance to host neutrophil extracellular traps. Sci. China Life Sci. 64, 621–632 (2021). https://doi.org/10.1007/s11427-020-1854-2

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  • DOI: https://doi.org/10.1007/s11427-020-1854-2

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