By visualizing DNA with diamidino phenylindole (DAPI), we found that hypothermal incubation followed by rewarming of human neutrophils resulted in an increased number of DAPI-positive objects representative of extensi...By visualizing DNA with diamidino phenylindole (DAPI), we found that hypothermal incubation followed by rewarming of human neutrophils resulted in an increased number of DAPI-positive objects representative of extensive DNA unfolding seemingly similar to neutrophil extracellular traps (NETs). In contrast to canonical NET formation, diphenylene iodonium (DPI), an NADPH oxidase inhibitor, exhibited negligible effects on formation of the DAPI-positive objects. Moreover, multiple instances of DNA damage were detected in the objects, but not in canonical NETs. Our results thus suggest the potential of hypothermia for triggering DNA structural alteration in neutrophils, which is similar to but distinct from NET formation.展开更多
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 r...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 Tat D 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 Tat D 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 Tat D DNases to degrade NETs.展开更多
文摘By visualizing DNA with diamidino phenylindole (DAPI), we found that hypothermal incubation followed by rewarming of human neutrophils resulted in an increased number of DAPI-positive objects representative of extensive DNA unfolding seemingly similar to neutrophil extracellular traps (NETs). In contrast to canonical NET formation, diphenylene iodonium (DPI), an NADPH oxidase inhibitor, exhibited negligible effects on formation of the DAPI-positive objects. Moreover, multiple instances of DNA damage were detected in the objects, but not in canonical NETs. Our results thus suggest the potential of hypothermia for triggering DNA structural alteration in neutrophils, which is similar to but distinct from NET formation.
基金supported by the Distinguished Scientist grant from Shenyang Agricultural University and Liaoning Province(8804880416076)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-042)。
文摘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 Tat D 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 Tat D 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 Tat D DNases to degrade NETs.
