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

Zhiguang Chang,Qijun Chen,Jigang Yin,Ning Jiang,Xunjia Cheng,Huijun Lu,Yuanyuan Zhang,Yaming Cao,Mats Wahlgren

doi:10.1038/ncomms11537

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.

Highlights

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
These filamentous structures are known as neutrophil extracellular traps (NETs) and have been demonstrated to contribute to pathogen capture as part of the innate immune response[3,4]
Plasma haem can induce the formation of NETs in vitro[11], and haem is abundantly released in the host-blood circulation on the rupture of Plasmodium falciparum-infected erythrocytes[12,13]

Summary

Introduction

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. On activation by initial microbial contact, neutrophils and macrophages export filamentous elements composed of DNA and proteases, which confine the invading pathogens[1,2] These filamentous structures are known as neutrophil extracellular traps (NETs) and have been demonstrated to contribute to pathogen capture as part of the innate immune response[3,4]. We identify a DNase sequence in Plasmodium falciparum that contains a signal peptide and is homologous to bacterial TatD DNases ( named TatD-like DNases) that are actively expressed in both P. falciparum and in rodent malarial parasites The expression of this TatD-like DNase is associated with parasite virulence, and TatD-like DNase-specific antibodies are key elements in providing anti-plasmodium immunity

Methods

Results

Conclusion