Characteristics of dengue virus-infected peripheral blood mononuclear cell death that correlates with the severity of illness
Article first published online: 28 APR 2009
© 2009 The Societies and Blackwell Publishing Asia Pty Ltd
Microbiology and Immunology
Volume 53, Issue 8, pages 442–450, August 2009
How to Cite
Jaiyen, Y., Masrinoul, P., Kalayanarooj, S., Pulmanausahakul, R. and Ubol, S. (2009), Characteristics of dengue virus-infected peripheral blood mononuclear cell death that correlates with the severity of illness. Microbiology and Immunology, 53: 442–450. doi: 10.1111/j.1348-0421.2009.00148.x
- Issue published online: 22 JUL 2009
- Article first published online: 28 APR 2009
- Received 17 February 2009; revised 5 April 2009; accepted 10 April 2009.
- cDNA microarray analysis;
- dengue hemorrhagic fever/dengue shock syndrome;
- dengue virus;
- receptor-mediated death
The pathogenic mechanism of the severe form of dengue is complicated. Recent reports indicate that apoptotic death of various tissues or organs may be associated with vascular leakage, and ultimately leads to the death of DENV-infected patients. In the present study, we provide additional evidence supporting the detrimental role of apoptosis in DENV infection. A comparison of the rate of apoptosis in PBMCs isolated from patients suffering DF, a mild form of the disease, and the rate in patients with DHF, a life-threatening disease, revealed that PBMCs from DHF patients underwent apoptosis at a significantly higher rate than those suffering from DF alone. This suggests that the severity of natural DENV infection correlates with PBMC apoptosis. In addition, this cell death was induced not only by DENV itself, but also by the apoptotic activities of pro-inflammatory cytokines, such as TNF-α, and IL-1β, that were upregulated in DHF patients. The death of these mononuclear cells that function in an innate immune system may explain the higher viral load in DHF patients than in DF patients. Interestingly, a gene expression profile pattern elucidated that apoptosis occurring during natural DENV infection involved mainly the extrinsic apoptosis pathway, which is mediated via both caspase-dependent and caspase-independent mechanisms. In conclusion, our data highlight the adverse effect of apoptosis induced by DENV and by pro-inflammatory cytokines during natural DENV infection.