title: The TatD-like DNase of Plasmodium is a virulence factor and a potential malaria vaccine candidate.
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.
authors.affiliation: Key Laboratory of Zoonosis, Jilin University, Xi An Da Lu 5333, Changchun 130062, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Key Laboratory of Zoonosis, Jilin University, Xi An Da Lu 5333, Changchun 130062, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Zoonosis, Jilin University, Xi An Da Lu 5333, Changchun 130062, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Zoonosis, Jilin University, Xi An Da Lu 5333, Changchun 130062, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Lu
authors.affiliation: Key Laboratory of Zoonosis, Jilin University, Xi An Da Lu 5333, Changchun 130062, China.
authors.forename: Jigang
authors.initials: J
authors.lastname: Yin
authors.affiliation: Institute of Microbiology, Tumour and Cellular Biology, Karolinska Institutet, Nobels väg 16, S-171 77 Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Wahlgren
authors.affiliation: Department of Pathogen Biology, Fudan University, Handan Road 220, Shanghai 200433, China.
authors.forename: Xunjia
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Immunology, China Medical University, Puhe Road 77, Shenyang 110122, China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Key Laboratory of Zoonosis, Jilin University, Xi An Da Lu 5333, Changchun 130062, China.|Institute of Microbiology, Tumour and Cellular Biology, Karolinska Institutet, Nobels väg 16, S-171 77 Stockholm, Sweden.|Key Laboratory of Zoonosis, Shenyang Agricultural University, Dongling Road 120, Shenyang 10866, China.
authors.forename: Qijun
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D003851:Deoxyribonucleases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D065206:Extracellular Traps / Q000276:immunology*; D055786:Gene Knockout Techniques; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000517:prevention & control; D051379:Mice; D010962:Plasmodium berghei / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D015696:Gene Products, tat; D017780:Malaria Vaccines; D037521:Virulence Factors; D003851:Deoxyribonucleases