title: Excessive proinflammatory cytokine and chemokine responses of human monocyte-derived macrophages to enterovirus 71 infection.
abstract: 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.
authors.affiliation: School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xun
authors.initials: X
authors.lastname: Gong
authors.forename: Jianfang
authors.initials: J
authors.lastname: Zhou
authors.forename: Wenfei
authors.initials: W
authors.lastname: Zhu
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis; D029821:Enterovirus A, Human / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D016207:Cytokines; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1