Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

Abstract

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 (r s = 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. supervision, C.S., D.N. and L.E.M.; project administration, J.S.; funding, D.A., B.H.S., D.N., L.E.M. and C.S.; acquisition, D.A., L.E.M., C.S. and J.S. All authors have read and agreed to the published version of the manuscript.

A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes’ interactions points to Neutrophil extracellular traps as mediators of thrombosis in COVID-19

“…NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases with reports now emerging that describe their presence in COVID-19[ 9 , 61 – 63 ]. Amongst the known diseases associated with NETs, several are related to children including Cystic Fibrosis [ 64 ], Meningococcal Sepsis [ 65 ]; Lyme Neurobiellosis [ 66 ]; Juvenile Dermatomyositis [ 67 ] and pediatric inflammatory bowel diseases [ 68 ]. In pediatric sepsis, NETs levels were elevated and correlated with disease severity, mirroring results in mice where higher NETs levels in response to lipopolysaccharides are found in infant mice compared to adults [ 69 ].…”

A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes’ interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19

“…NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases with reports now emerging that describe their presence in COVID-19 9,54–56 . Amongst the known diseases associated with NETs, several are related to children including Cystic Fibrosis 57 , Meningococcal Sepsis 58 ; Lyme Neurobiellosis 59 ; Juvenile Dermatomyositis 60 and pediatric inflammatory bowel diseases 61 . In pediatric sepsis, NETs levels were elevated and correlated with disease severity, mirroring results in mice where higher NETs levels in response to lipopolysaccharides are found in infant mice compared to adults 62 .…”

Increase of Neutrophil Extracellular Traps, Mitochondrial DNA and Nuclear DNA in Newly Diagnosed Type 1 Diabetes Children but Not in High-Risk Children

“…A NET-remnants ELISA, detecting complexes of DNA and myeloperoxidase (MPO) both found in NETs, was run for all samples (cohort 1-3) as previously described ( 29 ). NET-remnants will be referred to as NETs for the rest of the article.…”