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http://ir.nhri.org.tw/handle/3990099045/8343
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| Title: | Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns |
| Authors: | Hsiao, HB;Chou, AH;Lin, SI;Chen, IH;Lien, SP;Liu, CC;Chong, P;Liu, SJ |
| Contributors: | Division of Vaccine Research and Development |
| Abstract: | Enterovirus 71 (EV71), a positive-stranded RNA virus, is the major cause of hand, foot, and mouth disease (HFMD) with severe neurological symptoms. Antiviral type I interferon (alpha/beta interferon [IFN-α/β]) responses initiated from innate receptor signaling are inhibited by EV71-encoded proteases. It is less well understood whether EV71-induced apoptosis provides a signal to activate type I interferon responses as a host defensive mechanism. In this report, we found that EV71 alone cannot activate Toll-like receptor 9 (TLR9) signaling, but supernatant from EV71-infected cells is capable of activating TLR9. We hypothesized that TLR9-activating signaling from plasmacytoid dendritic cells (pDCs) may contribute to host defense mechanisms. To test our hypothesis, Flt3 ligand-cultured DCs (Flt3L-DCs) from both wild-type (WT) and TLR9 knockout (TLR9KO) mice were infected with EV71. More viral particles were produced in TLR9KO mice than by WT mice. In contrast, alpha interferon (IFN-α), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-α), IFN-γ, interleukin 6 (IL-6), and IL-10 levels were increased in Flt3L-DCs from WT mice infected with EV71 compared with TLR9KO mice. Seven-day-old TLR9KO mice infected with a non-mouse-adapted EV71 strain developed neurological lesion-related symptoms, including hind-limb paralysis, slowness, ataxia, and lethargy, but WT mice did not present with these symptoms. Lung, brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice exhibited significantly higher viral loads than equivalent tissues collected from WT mice. Histopathologic damage was observed in brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice infected with EV71. Our findings demonstrate that TLR9 is an important host defense molecule during EV71 infection. |
| Date: | 2014-07-30 |
| Relation: | Journal of Virology. 2014 Jul 30;88(20):11658-11670. |
| Link to: | http://dx.doi.org/10.1128/JVI.00867-14 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-538X&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000342688000004 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84907908055 |
| Appears in Collections: | [劉士任] 期刊論文
[莊再成] 期刊論文
[劉家齊] 期刊論文
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| SCP84907447037.pdf | | 2311Kb | Adobe PDF | 590 | View/Open |
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