Excessive proinflammatory cytokine and chemokine responses of human monocyte-derived macrophages to enterovirus 71 infection

BMC Infectious Diseases

Zhaojun Duan¹  Yu Jin²  Lili Li¹  Jinsong Li¹  Na Liu¹  Wenfei Zhu¹  Jianfang Zhou¹  Xun Gong¹ 

[1] National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 100052, PR China;Nanjingn Children’s Hospital, Medical School of Nanjing University, Nanjing, 210093, PR China

关键词: Toll-like receptors;    Chemokines;    Proinflammatory cytokines;    Macrophages;    Enterovirus 71;   

Others  :  1159674
DOI  :  10.1186/1471-2334-12-224

 received in 2012-01-13, accepted in 2012-08-31,  发布年份 2012

【 摘 要 】

Background

The levels of proinflammatory cytokine or chemokine in blood and cerebrospinal fluid are thought to be one of predictors for clinical severity of enterovirus 71 (EV71) infection, yet the cellular sources or signalling mechanism remain undefined. Here, we focused on the response of human primary monocyte-derived macrophages (MDMs) to EV71 virus and its possible mechanisms.

Methods

Human primary MDMs were infected by EV71 virus in vitro. Infectivity and viral replication were assayed, and cytokine responses were determined by Cytometric Bead Array(CBA) analysis. The relative changes of Toll-like receptors, retinoic acid-inducible gene I (RIG-I) and melamoma differentiation associated gene 5 (MDA5) mRNA expression were detected by real-time RT-PCR.

Results

Effective infection and viral replication were detected in EV71-infected MDMs. The titters of progeny virus released from EV71-infected MDMs gradually increased from 6-h to 48-h point of infection (POI.). Proinflammatory cytokines: IL-1, IL-6, TNF-α but not IFN-α and γ were induced in MDMs by EV71. EV71 infection significantly increased the release of IL-8, IP-10 and RANTES at 12-h or 24-h POI. Upregulation of TLR2, TLR7 and TLR8 mRNA expression rather than TLR3, TLR4, TLR6, TLR9, TLR10, RIG-I, MDA5 were found at different time points in EV71-infected MDMs.

Conclusions

Our findings suggested that macrophages are not only the important target cells but also the effectors during EV71 infection, and they may play an important role in the pathogenesis of EV71 infection. And the proinflammatory cytokine and chemokine responses in EV71-infected MDMs may be mediated by the activation of differential pattern of TLRs.

【 授权许可】

   
2012 Gong et al.; licensee BioMed Central Ltd.

【 图 表 】

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