Enterovirus_71_Infection_of_Human_Dendritic_Cells.pdf

Enterovirus 71 Infection of Human Dendritic Cells YU-WEN LIN,* SHAINN-WEI WANG, YUK-YING TUNG, AND SHUN-HUA CHEN§,1 *Institute of Basic Biomedical Sciences, Institute of Molecular Medicine, §Department of Microbiology and Immunology, College of Medicine, and Statistical Analysis Laboratory, Institute of Education, College of Social Sciences, National Cheng Kung University, Tainan, Taiwan, 701, Republic of China Enterovirus 71 (EV71) causes death and long-term neurologic sequelae in hundreds of thousands of young children, but its pathogenesis remains elusive. Dendritic cells (DCs) play a crucial role in antiviral immunity by functioning as professional antigen-presenting cells to prime T cells and by secreting cytokines to modulate immune responses. Here, we show that EV71 productively infected human immature DCs and ex- pressed viral antigen in DCs. EV71 entry into DCs was partially mediated by DC-SIGN. Further analyses revealed that EV71 increased the viability, activation, release of cytokines, inter- leukin-6, interleukin-12, and tumor necrosis factor-a in DCs. Moreover, EV71 enabled DCs to stimulate T-cell proliferation. Collectively, these findings suggest that EV71 infection of human DCs in vivo is very likely to elicit protective immunity, because in infected mice, both T cells and IL-6 function to reduce mortality. Exp Biol Med 234:1166–1173, 2009 Key words: enterovirus 71; dendritic cells, and infection Introduction Enterovirus 71 (EV71), a neurotropic picornavirus, infects the human central nervous system and induces fatal neurological manifestations. Severe symptoms, such as brainstem encephalitis and cardiopulmonary complications, often cause death or long-term neurological sequelae, especially in young children (1–5). In the past decade, the Asia-Pacific region had more frequent and widespread EV71 outbreaks, which are estimated to have infected millions of children and have caused death and long-term neurological sequelae in hundreds of thousands