Plasmodium TatD-Like DNase Antibodies Blocked Parasite Development in the Mosquito Gut

Abstract

The TatD-like DNase of Plasmodium species has previously been characterized as a conserved antigen that plays an important role in immune evasion. Here, we found that TatD-like DNase is expressed, apart from the erythrocytic stage, throughout the developmental stages of the parasite in the mosquito vector. Antibodies to the molecule significantly blocked parasites development and transition in the mosquito gut. Further, mice immunized with recombinant TatD-like DNase showed significant resistance to parasite challenge. The antigenicity of the TatD-like antigen in combination with various adjuvants, including Freund’s adjuvants, Montanide ISA 51 and 61, Alhydrogel (aluminum hydroxide), and levamisole was investigated. It was found that immunization of the recombinant TatD-like DNase in combination with Montanide ISA 51 induced strong humoral responses that showed significant protection against parasite challenge in a mouse model. The data further support that TatD-like DNase is a functionally important molecule in the whole development cycle of the malaria parasites and a candidate for malaria vaccine development.

Characterization of Two Trichinella spiralis Adult-Specific DNase II and Their Capacity to Induce Protective Immunity

“…The Schistosoma japonicum DNase II contained a highly conserved catalytic domain, and rSjDNase II could degrade the genomic DNA and the elicited early humoral immune responses in mice ( Hou et al, 2015 ). A similar result was also observed in a previous study on Plasmodium TatD-like DNase; the immunization of mice with Plasmodium TatD-like DNase elicited strong humoral responses and obvious protection against challenge with malarial parasite, and TatD-like DNase specific antibodies distinctly interrupted the exflagellation of male gametocytes, ookinete, and oocyst formation in the mosquito’s gut ( Wang et al, 2018 ).…”

“…The neutralization of the DNase enzyme activity by DNase specific antibodies may enhance the macrophage’s adhering and decomposing abilities on the parasites. The immune protection conferred by immunizing with rTsDNase II could be also because of the TsDNase II-specific antibodies neutralizing the TsDNase II enzymatic activity to degrade the ETs formed by the macrophages-derived DNA, which resulted in the killing and destruction of the parasite, impeded worm development, and therefore reduced the worm burden ( Ortega-Pierres et al, 2015 ; Wang et al, 2018 ).…”

Global Lysine Crotonylation and 2-Hydroxyisobutyrylation in Phenotypically Different Toxoplasma gondii Parasites

“…First, the slides were blocked with 5% skim milk for 1 hour at 37 °C and then incubated with primary antibodies recognizing crotonyllysine (Cat#: PTM-502) and 2-hydroxybutyryllysine (Cat#: PTM-801) (PTM BIO) for 1 hour at 37 °C. Then, the cells were incubated for 30 min at 37 °C using a fluorescent secondary antibody (Thermo, MA), and the nuclei were stained as previously described (17, 18). High-resolution images were captured by a confocal laser scanning microscope (Leica, SP8, Wetzlar, Germany).…”

A structural study of TatD from Staphylococcus aureus elucidates a putative DNA-binding mode of a Mg2+-dependent nuclease

“…TatD is a protein that is widely presented and conserved in various species, both prokaryotes and eukaryotes (Wang et al, 2018), and it is also involved in the DNA-repair system, in apoptotic cell death and in cleaving neutrophil extracellular traps (Chang et al, 2016;Chen, Shen et al, 2014;Gannavaram & Debrabant, 2012;Qiu et al, 2005). A variety of genes encoding TatD-like proteins, including a single conserved TatD domain consisting of approximately 250 amino acids, have been reported (Chen, Li et al, 2014).…”