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* Department of Immunology, Division of Medicine, Hammersmith Hospital, Imperial College, London, United Kingdom;
Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand;
Division of Surgery, Oncology, Reproductive Biology and Anesthetics, Faculty of Medicine, Hammersmith Hospital, Imperial College, London, United Kingdom;
Pediatric Department, Khon Khan Hospital, Ministry of Public Health, Khon Kaen, Thailand;
¶ Department of Infection, University College London, Hamstead Campus, Rowland Hill Street, London, United Kingdom;
|| Medical Molecular Biology Unit, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; and
# Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
Severe dengue virus (DV) infections can cause the life-threatening condition dengue hemorrhagic fever, which is characterized by a severe plasma leak, thrombocytopenia, hemorrhage, and, in severe cases, circulatory collapse and death. There is now much evidence that pre-existing immunity to DV can enhance disease when an individual becomes infected on a second or sequential occasion. It has been shown that in contrast to infected dendritic cells (DC), noninfected bystander DC underwent maturation in dengue infection. In this study, we show that TNF-
and type I IFN contribute to the maturation of bystander DC, whereas the inhibition of DV-infected DC maturation can be overcome by activated T cells. Furthermore, IFN-
-inducible chemokines, CXCL9, 10, and 11 produced by infected DC are greatly amplified in the presence of DV-specific T cells. The chemokine secretion is also enhanced in coculture of HUVEC with either DV-infected DC or activated T cells. Finally, we found a close correlation between the serum level of these three chemokines and disease severity.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Medical Research Council, U.K.; the Wellcome Trust, U.K.; the National Institute for Health Research Biomedical Research Centre funding scheme; the Thailand Tropical Disease Research Program T2; and the Thailand National Centre for Genetic Engineering and Biotechnology.
2 Address correspondence and reprint requests to Dr. Gavin Screaton, Department of Immunology, Division of Medicine, Hammersmith Hospital, Imperial College, London W12 0NN, U.K.; E-mail address: g.screaton{at}imperial.ac.uk or Dr. Juthathip Mongkolsapaya, Department of Immunology, Division of Medicine, Hammersmith Hospital, Imperial College, London W12 0NN, United Kingdom; E-mail address: j.mongkolsapaya{at}imperial.ac.uk
3 Abbreviations used in this paper: DV, dengue virus; BFA, brefeldin A; DC, dendritic cell; DC-SIGN, DC-specific ICAM-grabbing nonintegrin; DF, dengue fever; DHF, dengue hemorrhagic fever; MFI, mean fluorescence intensity; NS1, nonstructural protein 1.
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