Neutrophil Extracellular Traps Contribute to the Disease Severity of Dengue Virus Infection
,
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.
1. Stanaway JD, Shepard DS, Undurraga EA, Halasa YA, Coffeng LE, Brady OJ, Hay SI, Bedi N, Bensenor IM, Castaneda-Or¬juela CA, Chuang TW, Gibney KB, Mem¬ish ZA, Rafay A, Ukwaja KN, Yonemo¬to N, Murray CJL (2016) The global bur¬den of dengue: an analysis from the Glob¬al Burden of Disease Study 2013. Lan¬cet Infect Dis. 16(6): 712–723.
2. Martina BE, Koraka P, Osterhaus AD (2009) Dengue virus pathogenesis: an integrat¬ed view. Clin Microbiol Rev. 22(4): 564–581.
3. Opasawatchai A, Amornsupawat P, Ji-ravejchakul N, Chan-In W, Spoerk NJ, Manopwisedjaroen K, Singhasivanon P, Yingtaweesak T, Suraamornkul S, Mongkolsa¬paya J, Sakuntabhai A, Ma-tangkasombut P, Loison F (2018) Neu-trophil Activation and Early Features of NET Formation Are Associated With Den¬gue Virus Infection in Human. Front Immunol. 9: 3007.
4. Schonrich G, Raftery MJ (2016) Neutro¬phil Extracellular Traps Go Viral. Front Immunol. 7: 366.
5. Ma Y, Yang X, Chatterjee V, Meegan JE, Beard RS, Jr., Yuan SY (2019) Role of Neutrophil Extracellular Traps and Ves-icles in Regulating Vascular Endothelial Permeability. Front Immunol. 10: 1037.
6. de Bont CM, Boelens WC, Pruijn GJM (2019) NETosis, complement, and coag-ulation: a triangular relationship. Cell Mol Immunol. 16(1): 19–27.
7. Devignot S, Sapet C, Duong V, Bergon A, Rihet P, Ong S, Lorn PT, Chroeung N, Ngeav S, Tolou HJ, Buchy P, Couis-sinier-Paris P (2010) Genome-wide ex-pres¬sion profiling deciphers host respons¬es altered during dengue shock syn¬drome and reveals the role of innate im¬munity in severe dengue. PLoS One. 5 (7): e11671.
8. Xie Z, Bailey A, Kuleshov MV, Clarke DJB, Evangelista JE, Jenkins SL, Lachmann A, Wojciechowicz ML, Kropiwnicki E, Jagod¬nik KM, Jeon M, Ma'ayan A (2021) Gene Set Knowledge Discovery with En¬richr. Curr Protoc. 1(3): e90.
9. Sung PS, Huang TF, Hsieh SL (2019) Ex-tracellular vesicles from CLEC2-activat-ed platelets enhance dengue virus-in-duced lethality via CLEC5A/TLR2. Nat Com¬mun. 10(1): 2402.
10. Garishah FM, Rother N, Riswari SF, Alis-jahbana B, Overheul GJ, van Rij RP, van der Ven A, van der Vlag J, de Mast Q (2021) Neutrophil Extracellular Traps in Dengue Are Mainly Generated NOX-Independently. Front Immunol. 12: 629167.
11. Fuchs TA, Bhandari AA, Wagner DD (2011) Histones induce rapid and pro-found thrombocytopenia in mice. Blood. 118(13): 3708–37014.
12. Boone BA, Murthy P, Miller-Ocuin J, Do-erfler WR, Ellis JT, Liang X, Ross MA, Wallace CT, Sperry JL, Lotze MT, Neal MD, Zeh HJ, 3rd (2018) Chloroquine re-duces hypercoagulability in pancreatic cancer through inhibition of neutrophil extracellular traps. BMC Cancer. 18(1): 678.
13. Gao Y, Zhang JG, Liu ZZ, Ma K, Lin XQ, Zhang JB, Chen W, Yang YJ (2022) Extracellular trap can be trained as a memory response. Virulence. 13(1): 471–482.
14. Soo KM, Khalid B, Ching SM, Chee HY (2016) Meta-Analysis of Dengue Sever-ity during Infection by Different Dengue Virus Serotypes in Primary and Second¬ary Infections. PLoS One. 11(5): e0154760.
15. Vicente CR, Herbinger KH, Froschl G, Mal¬ta Romano C, de Souza Areias Cabidelle A, Cerutti Junior C (2016) Serotype in¬fluences on dengue severity: a cross-sec¬tional study on 485 confirmed dengue cases in Vitoria, Brazil. BMC Infect Dis. 16: 320.
| Files | ||
| Issue | Articles In Press | |
| Section | Short Communication | |
| Keywords | ||
| Neutrophil extracellular traps; NETs; Neutrophil; Dengue | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
