The TatD-like DNase of Plasmodium is a virulence factor and a potential malaria vaccine candidate

Zhiguang Chang, Ning Jiang, Yuanyuan Zhang, Huijun Lu, Jigang Yin, Mats Wahlgren, Xunjia Cheng, Yaming Cao and Qijun Chen ()
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Zhiguang Chang: Key Laboratory of Zoonosis, Jilin University
Ning Jiang: Key Laboratory of Zoonosis, Jilin University
Yuanyuan Zhang: Key Laboratory of Zoonosis, Jilin University
Huijun Lu: Key Laboratory of Zoonosis, Jilin University
Jigang Yin: Key Laboratory of Zoonosis, Jilin University
Mats Wahlgren: Institute of Microbiology, Tumour and Cellular Biology, Karolinska Institutet
Xunjia Cheng: Fudan University
Yaming Cao: China Medical University
Qijun Chen: Key Laboratory of Zoonosis, Jilin University

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract Neutrophil extracellular traps (NETs), composed primarily of DNA and proteases, are released from activated neutrophils and contribute to the innate immune response by capturing pathogens. Plasmodium falciparum, the causative agent of severe malaria, thrives in its host by counteracting immune elimination. Here, we report the discovery of a novel virulence factor of P. falciparum, a TatD-like DNase (PfTatD) that is expressed primarily in the asexual blood stage and is likely utilized by the parasite to counteract NETs. PfTatD exhibits typical deoxyribonuclease activity, and its expression is higher in virulent parasites than in avirulent parasites. A P. berghei TatD-knockout parasite displays reduced pathogenicity in mice. Mice immunized with recombinant TatD exhibit increased immunity against lethal challenge. Our results suggest that the TatD-like DNase is an essential factor for the survival of malarial parasites in the host and is a potential malaria vaccine candidate.

Date: 2016
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DOI: 10.1038/ncomms11537

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