Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections
Daniel Appelgren,
Helena Enocsson,
Barbro H. Skogman,
Marika Nordberg,
Linda Perander,
Dag Nyman,
Clara Nyberg,
Jasmin Knopf,
Luis E. Muñoz,
Christopher Sjöwall,
Johanna Sjöwall
Affiliations
Daniel Appelgren
Division of Drug Research, Department of Medical and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden
Helena Enocsson
Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden
Barbro H. Skogman
Center for Clinical Research Dalarna-Uppsala University, Region Dalarna and Faculty of Medicine and Health Sciences, Örebro University, SE-702 81 Örebro, Sweden
Marika Nordberg
Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland
Linda Perander
Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland
Dag Nyman
Bimelix AB, AX-22 100 Mariehamn, Åland, Finland
Clara Nyberg
Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland
Jasmin Knopf
Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany
Luis E. Muñoz
Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany
Christopher Sjöwall
Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden
Johanna Sjöwall
Clinic of Infectious Diseases, Linköping University Hospital, SE-581 85 Linköping, Sweden
Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (rs = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.
