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

Cucunawangsih  Cucunawangsih; Ratna  Sari-Wijaya; Nata Pratama  Hardjo-Lugito; Ivet  Suriapranata

doi:10.18502/jad.v18i2.17540

Cucunawangsih Cucunawangsih Department of Microbiology, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia
Ratna Sari-Wijaya Department of Microbiology, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia
Nata Pratama Hardjo-Lugito Department of Internal Medicine, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia
Ivet Suriapranata Division of Immunology, Mochtar Riady Institute for Nanotechnology and Medical Science Group, Pelita Harapan University, Tangerang, Indonesia

DOI: https://doi.org/10.18502/jad.v18i2.17540

Keywords: Neutrophil extracellular traps; NETs; Neutrophil; Dengue

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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