TatD DNases of African trypanosomes confer resistance to host neutrophil extracellular traps

• DOI: 10.1007/s11427-020-1854-2
• Publication Date: 2021-01-09T11:47:15Z
• Authors: Kai Zhang; Ning Jiang; Hongyu Chen; Naiwen Zhang; Xiaoyu Sang; Ying Feng; Ran Chen; Qijun Chen
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Trypanosoma; Deoxyribonucleases; Sequence Homology, Amino Acid; Neutrophils; Trypanosoma brucei brucei; Protozoan Proteins; Extracellular Traps; Immunity, Innate; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Species Specificity; Host-Pathogen Interactions; Microscopy, Electron, Scanning; Animals; Female; Amino Acid Sequence; Microscopy, Immunoelectron; Protozoan Infections, Animal; Phylogeny; Immune Evasion

African trypanosomatid parasites escape host acquired immune responses through periodic antigenic variation of their surface coat. In this study, we describe a mechanism by which the parasites counteract innate immune responses. Two TatD DNases were identified in each of Trypanosoma evansi and Trypanosoma brucei. These DNases are bivalent metal-dependent endonucleases localized in the cytoplasm and flagella of the parasites that can also be secreted by the parasites. These enzymes possess conserved functional domains and have efficient DNA hydrolysis activity. Host neutrophil extracellular traps (NETs) induced by the parasites could be hydrolyzed by native and recombinant TatD DNases. NET disruption was prevented, and the survival rate of parasites was decreased, in the presence of the DNase inhibitor aurintricarboxylic acid. These data suggest that trypanosomes can counteract host innate immune responses by active secretion of TatD DNases to degrade NETs.