Neutrophil Extracellular Traps Contribute to the Disease Severity of Dengue Virus Infection

The spectrum of dengue infection ranges from asymptomatic or mild to severe disease. The pathogenic mechanisms are not fully understood. A viral infection can induce the neutrophil extracellular traps (NETs), and the excessive NETs lead to increased vascular permeability, coagulopathy, and platelet dysfunction, a hallmark of severe dengue.

To evaluate the association of NETs formation with disease severity using a human public transcriptomic dataset (GSE17924) and clinical samples from dengue patients with different disease severity.

Based on the transcriptomic analysis, the whole blood gene expression functional in neutrophil activities and NETs formation was upregulated with dengue disease severity. The serum concentration of citrullinated histone H3 (CitH3), a NETs marker, was measured in 28 dengue patients, of whom 18 classified as dengue fever (DF) and 10 as dengue hemorrhagic fever (DHF) grade 1 and 2. A significantly higher CitH3 concentration was found in DHF compared to DF patients. The level of CitH3 was negatively correlated with platelet counts.

Our results suggest NETs have contributed to the disease severity of dengue infection. Future studies on the predictive value of NETs markers and the potential NETs as a targeted therapy in dengue disease should be prioritized.