Neutrophil Extracellular Traps in the Rhesus Macaque Model of Ebolavirus Disease

Neutrophil extracellular traps (NETs) are one of several mechanisms neutrophils employ in response to microbial infection and are composed of decondensed chromatin studded with antimicrobial peptides and proteases that have been expelled to the extracellular space. In the 15 years since they were first identified for their antibacterial effects, NETs have also been implicated in the exacerbation of both infectious and non-infectious diseases through the development of coagulation disorders, tissue destruction, organ dysfunction, auto-antibodies, and the perpetuation of a hyper-inflammatory state. Several of these pathologies are consistent with those observed in Ebolavirus disease, e.g. coagulation disorders and organ dysfunction. In order to investigate whether NETs form in the context of Ebolavirus disease, multiple means of interrogation aimed at detecting markers of NETs in plasma and tissues derived from Ebola-infected Rhesus macaques were developed, including detection of MPO-DNA complexes and citrullinated histone H3 via sandwich ELISA as well as immunofluorescence assay for the detection of co-localized decondensed chromatin, citrullinated histone H3, and neutrophil elastase in tissue samples. Preliminary data indicate NETs do form in the context of Ebola infection beginning at 5 days post-infection in the Rhesus macaque, suggesting a potential role for NETs in Ebolavirus disease pathology.