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

Nat Commun. 2016 May 6:7:11537. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Deoxyribonucleases / genetics
  • Deoxyribonucleases / immunology*
  • Deoxyribonucleases / metabolism
  • Extracellular Traps / immunology*
  • Gene Knockout Techniques
  • Gene Products, tat / genetics
  • Gene Products, tat / immunology*
  • Gene Products, tat / metabolism
  • Malaria Vaccines
  • Malaria, Falciparum / prevention & control
  • Mice
  • Plasmodium berghei / genetics
  • Plasmodium berghei / immunology
  • Plasmodium berghei / metabolism
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology
  • Plasmodium falciparum / metabolism
  • Vaccination
  • Virulence Factors / genetics
  • Virulence Factors / immunology*
  • Virulence Factors / metabolism

Substances

  • Gene Products, tat
  • Malaria Vaccines
  • Virulence Factors
  • Deoxyribonucleases