作者
Naphak Modhiran, Daniel Watterson, David A Muller, Adele K Panetta, David P Sester, Lidong Liu, David A Hume, Katryn J Stacey, Paul R Young
发表日期
2015/9/9
期刊
Science translational medicine
卷号
7
期号
304
页码范围
304ra142-304ra142
出版商
American Association for the Advancement of Science
简介
Complications arising from dengue virus infection include potentially fatal vascular leak, and severe disease has been linked with excessive immune cell activation. An understanding of the triggers of this activation is critical for the development of appropriately targeted disease control strategies. We show here that the secreted form of the dengue virus nonstructural protein 1 (NS1) is a pathogen-associated molecular pattern (PAMP). Highly purified NS1 devoid of bacterial endotoxin activity directly activated mouse macrophages and human peripheral blood mononuclear cells (PBMCs) via Toll-like receptor 4 (TLR4), leading to the induction and release of proinflammatory cytokines and chemokines. In an in vitro model of vascular leak, treatment with NS1 alone resulted in the disruption of endothelial cell monolayer integrity. Both NS1-mediated activation of PBMCs and NS1-induced vascular leak in vitro were …
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N Modhiran, D Watterson, DA Muller, AK Panetta… - Science translational medicine, 2015