Neutrophils have an important role in rapid antimicrobial defenses against and resolution of urinary tract infections (UTIs). We show that a mechanism known as neutrophil extracellular trap (NET) formation is a strategy to combat pathogens in the urinary tract. Viscous aggregates that were present in human urine sediments revealed high extracellular DNA content. The DNA formed a scaffold to which antimicrobial effector proteins derived from different neutrophil subcellular compartments bound. Treatment with deoxyribonuclease I solubilized these structures. We observed massive proteolytic degradation in the NETs with apparently dominant roles for the neutrophil granule proteases elastase, proteinase 3, and cathepsin G. In a UTI case with Staphylococcus aureus as the infectious agent, high abundance of autolysins and immune evasion factors in a cell-free NET extract suggested that controlled cell wall autolysis plays a role in derailing the host immune response and allows some bacterial cells to survive following entrapment in NETs.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Urine ; Proteomics ; LCMSMS ; Neutrophil Extracellular Traps (NETs) ; Urinary Tract Infection (UTI)
Principal Investigators: (in alphabetical order) |
Yanbao Yu, J. Craig Venter Institute, Rockville MD 20850 USA, N/A |
Submitting User: | ccms |
Yu Y, Kwon K, Tsitrin T, Bekele S, Sikorski P, Nelson KE, Pieper R.
Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections.
PLoS Pathog. 2017 Jan;13(1):e1006151. Epub 2017 Jan 27.
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