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and TLR Ligands1
* Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand;
Department of Immunology and Medicine and
Department of Enteric Diseases, U.S. Army Medical Component of the Armed Forces Research Institute of the Medical Sciences, Bangkok, Thailand; and
Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
There is worldwide concern that the avian influenza H5N1 virus, with a mortality rate of >50%, might cause the next influenza pandemic. Unlike most other influenza infections, H5N1 infection causes a systemic disease. The underlying mechanisms for this effect are still unclear. In this study, we investigate the interplay between avian influenza H5N1 and human dendritic cells (DC). We showed that H5N1 virus can infect and replicate in monocyte-derived and blood myeloid DC, leading to cell death. These results suggest that H5N1 escapes viral-specific immunity, and could disseminate via DC. In contrast, blood pDC were resistant to infection and produced high amounts of IFN-
. Addition of this cytokine to monocyte-derived DC or pretreatment with TLR ligands protected against infection and the cytopathic effects of H5N1 virus.
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 National Center for Genetic Engineering and Biotechnology (BIOTEC) Thailand, the Ellison Medical Foundation prime grant, by Thailand Research Fund for Advanced Research Scholar, and by Grant Y1-AI-5026-01 from the National Institutes of Health, National Institute of Allergy and Infectious Diseases International Research in Infectious Disease.
2 Address correspondence and reprint requests to Dr. Sathit Pichyangkul, Department of Immunology and Medicine, U.S. Army Medical Component of the Armed Forces Research Institute of the Medical Sciences, 315/6 Rajvithi Road, Bangkok 10400, Thailand. E-mail address: sathitp{at}afrims.org
3 Abbreviations used in this paper: DC, dendritic cell; mDC, myeloid DC; pDC, plasmacytoid DC; MOI, multiplicity of infection.
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