Dewa Ayu Putri Sri Masyeni, Usman Hadi, Kuntaman Kuntaman, Benediktus Yohan, Nur Ita Margyaningsih, R Tedjo Sasmono

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Overproduction of numerous pro-inflammatory cytokines, during dengue virus (DENV) infection, has been related to plasma leakage in the vascular endothelium and studied elsewhere with conflicting results. The current study objective is to evaluate the expression of four cytokine/chemokine genes following DENV-2 infection within peripheral blood mononuclear cells (PBMC) isolated from a healthy donor. Venous blood was drawn,  and PBMCs were isolated using Ficoll density gradient centrifugation. Cells were maintained in culture medium and infected with Indonesian isolate of DENV-2. Cells were harvested and followed by total RNA extraction and reverse-transcription into cDNA using oligo d(T) primers and Reverse Transcriptase enzyme system. The SYBR Green-based quantitative qRT-PCR was used to calculate the relative expression of IL-6, IL-8, IP-10 and MIP-1β- encoding genes during infection time points, compared to uninfected cell controls. The observation of the cytokine was on the 6 and 18 hours post-infection. The different expression profiles of cytokines/chemokines were observed. The up-regulation of gene expression was observed for IL-8 and IP-10. In contrast, the down-regulatory of IL-6 and MIP-1β genes expression was documented during the infection period. The cytokine IL-8 and IP-10 are potent chemoattractants  in the recruitment  of neutrophil, basophil, and lymphocytes in response to an infection. The highlight of this study is on the up-regulation of IL-8 and IP-10 genes expression which may confirm the roles of these chemokines in the pathogenesis of dengue infection.


dengue, gene expression, cytokine, chemokine, PBMC

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Ooi E-E, Gubler DJ. Dengue in Southeast Asia: epidemiological characteristics and strategic challenges in disease prevention. Cad Saude Publica. 2009;25:S115–24.

Murray NEA, Quam MB, Wilder-Smith A. Epidemiology of dengue: past, present and future prospects. Clin Epidemiol. 2013;5:299–309.

Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. Dengue: A continuing global threat. Nat Rev Microbiol. 2010;8(12):S7–16.

Guzman MG, Harris E. Dengue. Lancet. 2015;385(9966):453–65.

Katzelnick LC, Harris E, Baric R, Coller B-A, Coloma J, Crowe Jr JE, et al. Immune correlates of protection for dengue: State of the art and research agenda. Vaccine. 2017;35(36):4659–69.

Martina BEE, Koraka P, Osterhaus ADME. Dengue virus pathogenesis: An integrated view. Vol. 22, Clinical Microbiology Reviews. 2009. p. 564–81.

WHO. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever [Internet]. WHO Regional Publication SEARO. 2011. 159-168 p. Available from:

Srikiatkhachorn A, Mathew A, Rothman AL. Immune-mediated cytokine storm and its role in severe dengue. Semin Immunopathol. 2017 Jul;39(5):563–74.

Basu A, Chaturvedi UC. Vascular endothelium: The battlefield of dengue viruses. Vol. 53, FEMS Immunology and Medical Microbiology. 2008. p. 287–99.

Mangione JNA, Huy NT, Lan NTP, Mbanefo EC, Ha TTN, Bao LQ, et al. The association of cytokines with severe dengue in children. Trop Med Health. 2014 Dec;42(4):137–44.

Rathakrishnan A, Wang SM, Hu Y, Khan AM, Ponnampalavanar S, Lum LCS, et al. Cytokine Expression Profile of Dengue Patients at Different Phases of Illness. PLoS One. 2012;7(12).

Puerta-Guardo H, Sandino AR, González-Mariscal L, Rosales VH, Ayala-Dávila J, Chávez-Mungía B, et al. The cytokine response of U937-derived macrophages infected through antibody dependent enhancent of dengue virus disrupts cell apical junctional complexes and increase vascular permeability. J Virol. 2013;JVI-00085.

Yohan B, Kendarsari RI, Mutia K, Bowolaksono A, Harahap AR, Sasmono RT. Growth characteristics and cytokine/chemokine induction profiles of dengue viruses in various cell lines. Acta Virol. 2014;58(1):20–7.

Costa VV, Fagundes CT, Souza DG, Teixeira MM. Inflammatory and innate immune responses in dengue infection: protection versus disease induction. Am J Pathol. 2013 Jun;182(6):1950–61.

Bozza FA, Cruz OG, Zagne SMO, Azeredo EL, Nogueira RMR, Assis EF, et al. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC Infect Dis. 2008;8:1–11.

Fahri S, Yohan B, Trimarsanto H, Sayono S, Hadisaputro S, Dharmana E, et al. Molecular surveillance of dengue in semarang, indonesia revealed the circulation of an old genotype of dengue virus serotype-1. PLoS Negl Trop Dis. 2013 Aug;7(8):e2354.

Griffith JW, Sokol CL, Luster AD. Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol. 2014;32:659–702.

Tsai YT, Chang SY, Lee CN, Kao CL. Human TLR3 recognizes dengue virus and modulates viral replication in vitro. Cell Microbiol. 2009;11(4):604–15.

Becerra A, Warke K, Xhaja K, de Bosch N, Rothman AL, Bosch I. Gene expression profiling of dengue infected human primary cells identifies secreted mediators in vivo. J Med Virol. 2009 Aug;81(8):1403–11.

Ubol S, Masrinoul P, Chaijaruwanich J, Kalayanarooj S, Charoensirisuthikul T, Kasisith J. Differences in global gene expression in peripheral blood mononuclear cells indicate a significant role of the innate responses in progression of dengue fever but not dengue hemorrhagic fever. J Infect Dis. 2008 May;197(10):1459–67.

Fink J, Gu F, Ling L, Tolfvenstam T, Olfat F, Chin KC, et al. Host gene expression profiling of dengue virus infection in cell lines and patients. PLoS Negl Trop Dis. 2007;1(2):e86.

Kanwal F, Lu C, Qadri I, Sohail M, Zia-ur-Rahman F. Interleukin-6; A promising disease severity index for dengue virus infection. Asian Pacific J Trop Dis. 2017;7(5):266–9.

Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro-and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta (BBA)-Molecular Cell Res. 2011;1813(5):878–88.

Chen J, Ng MML, Chu JJH. Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection. PLoS Pathog. 2015;11(7).

Lee YH, Leong W-Y, Wilder-Smith A. Markers of dengue severity: a systematic review of cytokines and chemokines. J Gen Virol. 2016;97(12):3103–19.

Huang YH, Lei HY, Liu HS, Lin YS, Liu CC, Yeh TM. Dengue virus infects human endothelial cells and induces IL-6 and IL-8 production. Am J Trop Med Hyg. 2000;63:71–5.


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