Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 陈基湘教授 (微生物学系) |
| 黄曦教授 (内科及药物治疗学系) |
| 朱逸骏先生 (内科及药物治疗学系) |
| 陈子蔚教授 (微生物学系) |
| 魏莉嘉博士 (微生物学系) |
| 李嘉慧博士 (内科及药物治疗学系) |
| 许树昌教授 (内科及药物治疗学系) |
| 黄振国教授 (化学病理学系) |
| 李礼舜教授 (内科及药物治疗学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1111/irv.12109 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/24WOS source URL
Scopushttp://aims.cuhk.edu.hk/converis/portal/Publication/14Scopus source URL
其它资讯
摘要Background: We investigated the roles of Toll-like receptors (TLRs) in naturally occurring influenza. Methods: A prospective, case - control study was conducted. Adults hospitalized with virologically confirmed influenza A infections (onset <48 hours, before treatment) were compared with age-/gender-matched controls. TLRs (2, 3, 4, 7, 8, 9) expression in monocytes and dendritic cells (DCs - total, myeloid, plasmacytoid) was quantitated using flow cytometry. Gene expression of RLRs (RIG-1, MDA-5) was evaluated using real-time PCR. Concomitant signaling molecules expression, plasma cytokine/chemokine concentrations, and respiratory tract viral loads were measured. PBMCs were cultured and stimulated ex vivo with TLR-specific ligands for cytokine responses. Results: Forty two patients with influenza (http://aims.cuhk.edu.hk/converis/portal/Publication/24 A/H3N2, 18 A/H1N1pdm09) and 20 controls were studied. Patients' mean age was 68 ± 16 years; 81% had respiratory/cardiovascular complications. There were increased cellular expressions of TLR9, TLR8, TLR3, and TLR7 during influenza; TLR2 and TLR4 were suppressed. Results were similar for both virus strains. Higher TLR expression levels at presentation significantly correlated with lower viral loads (Spearman's rho: -0·46 to -0·69 for TLR9, TLR8, and TLR3; P-values <0·05). Multivariate regression models (adjusted for age, comorbidity, disease severity, time from onset) confirmed their independent associations. Increased signaling molecules (phospho-MAPKs, IκB) and inflammatory cytokines (IL-6, sTNFR-1, CCL2/MCP-1; CXCL10/IP-10, IFN-γ) correlated with increased TLR expression. RLRs were upregulated simultaneously. PBMCs of patients with influenza showed significant, dynamic changes in their cytokine responses upon TLR stimulation, compared with controls. Conclusions: Our results suggest that TLRs play an important role in early, innate viral inhibition in naturally occurring influenza. Inflammatory cytokine responses are concomitantly induced. These findings support investigation of TLR targeting as a novel intervention approach for prophylaxis against influenza. ? 2013 John Wiley & Sons Ltd.
着者Lee N., Wong C.K., Hui D.S.C., Lee S.K.W., Wong R.Y.K., Ngai K.L.K., Chan M.C.W., Chu Y.J., Ho A.W.Y., Lui G.C.Y., Wong B.C.K., Wong S.H., Yip S.P., Chan P.K.S.
期刊名称Influenza and Other Respiratory Viruses
出版年份2013
月份9
日期1
卷号7
期次5
出版社Blackwell Publishing Inc.
出版地United Kingdom
页次666 - 675
国际标準期刊号1750-2640
电子国际标準期刊号1750-2659
语言英式英语
关键词Influenza, Toll-like receptors
