标题: 上海巴斯德所手足口病免疫致病机理研究取得新进展 [打印本页] 作者: rentianyixu 时间: 2015-9-1 19:20 标题: 上海巴斯德所手足口病免疫致病机理研究取得新进展 8月19日，国际知名学术杂志Journal of Virology在线发表了中科院上海巴斯德研究所冷启彬课题组的研究论文“Type I interferons triggered through the TLR3-TRIF pathway control Coxsackievirus A16 infection in young mice” 。
作者: rentianyixu 时间: 2015-9-1 19:21
J Virol. 2015 Aug 19. pii: JVI.01627-15. [Epub ahead of print]
Type I interferons triggered through the TLR3-TRIF pathway control Coxsackievirus A16 infection in young mice.
Yang J1, Yang C1, Guo N1, Zhu K1, Kaiming L1, Zhang N1, Zhao H2, Cui Y1, Chen L3, Wang H3, Gu J4, Ge B5, Cheng-Feng Q2, Leng Q6.
Author information
1Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
3International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China.
4State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
5Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai, China.
6Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China qbleng@sibs.ac.cn.
Abstract
Coxsackievirus A16 (CVA16) is one of the major etiological agents that cause hand, foot and mouth disease (HFMD) in children. The host defense mechanisms against CVA16 infection remain almost entirely unknown. Unlike previous observations with EV71 infection, here we show that IFN-γ or iNKT cell deficiency did not affect the disease development and survival of CVA16-infected mice. In contrast, type I interferon receptor deficiency resulted in mice developing more severe disease, and they had a lower survival rate than wild-type mice. Similarly, deficiency of TLR3 and TRIF, but not other pattern recognition receptors, led to decreased survival of CVA16-infected mice. TLR3-TRIF signaling was indispensable for the induction of type I interferons during CVA16 infection in mice and protected young mice from disease caused by the infection. In particular, TRIF-mediated immunity was critical for preventing CVA16 replication in the neuronal system before disease occurred. IFN-β treatment was also found to compensate for TRIF deficiency in mice and decreased disease severity and mortality of CVA16-infected mice. Altogether, type I interferons induced by TLR3-TRIF signaling mediate protective immunity against CVA16 infection. These findings may shed light on therapeutic strategies to combat HFMD caused by CVA16 infection.
IMPORTANCE:
Hand, foot and mouth disease (HFMD) is a major threat to public health in the Asia-Pacific region. Both CVA16 and EV71 are major pathogens that are responsible for HFMD. The majority of research efforts have focused on the more virulent EV71 but little has been done with CVA16. Thus far, host immune responses to CVA16 infection have not yet be elucidated. The present study discovered an initial molecular mechanism underlying host protective immunity against CVA16 infection, providing the first explanation for why CVA16 and EV71 cause different clinical outcomes upon infection of humans. Therefore, different therapeutic strategies should be developed to treat HFMD cases caused by these two viruses.