Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Yanbao Yu  

PROVIDER: MSV000080847 | MassIVE | Fri Mar 31 22:13:00 BST 2017

SECONDARY ACCESSION(S): PXD005688

REPOSITORIES: MassIVE