Modulation of TLR9 response in a mouse model of herpes simplex virus encephalitis
Modulation of TLR9 response in a mouse model of herpes simplex virus encephalitis
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DOI：
10.1016/j.antiviral.2012.09.022
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发表时间：
2012-12-01
影响因子：
7.6
通讯作者：
Boivin, Guy
中科院分区：
文献类型：
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作者：
Boivin, Nicolas;Menasria, Rafik;Boivin, Guy
我们评估了Toll样受体（TLR）9的激动剂和拮抗剂与TLR 3激动剂在单纯疱疹病毒1型（HSV-1）脑炎（HSE）小鼠模型中的作用。BALB/c小鼠在HSV-1感染前1天接受单次鼻内剂量的TLR 3激动剂（聚肌苷酸：聚胞苷酸; PIC）、TLR 9激动剂（寡脱氧核苷酸（ODN）1585、1826或2395）或TLR 9拮抗剂（ODN 2088），对于选定组，在HSV-1感染后3天接受单次鼻内剂量的TLR 3激动剂（聚肌苷酸：聚胞苷酸; PIC）、TLR 9激动剂（寡脱氧核苷酸（ODN）1585、1826或2395）或TLR 9拮抗剂（ODN 2088）。在感染前接受媒介物、PIC、ODN 1585、1826、2395和2088预处理的小鼠分别具有25%、65%、55%、40%、55%和30%的存活率（PIC和ODN 1585和2395相对于媒介物的P < 0.05）。随后用媒介物处理感染的小鼠。ODN 2395和2088的存活率分别为9%、0%和30%（P < 0.05，ODN 2088与其他组相比）。用ODN 2395预处理小鼠降低了病毒载量（在第5天P < 0.05）和在第3、4和5天CCL 2、IL-6和CCL 5的产生（在第3天IL-6 P < 0.05，在第4天CCL 2和CCL 5 P < 0.05）。用ODN 2088治疗感染的小鼠减少了相同细胞因子的产生（在第5天，对于CCL 2 P = 0.07，对于IL-6 P = 0.09）。在感染前用TLR 9激动剂预处理小鼠降低了脑病毒载量和细胞因子水平，导致HSE存活率增加。另一方面，TLR 9拮抗剂可以有助于控制感染后可能有害的炎症反应。(C)2012爱思唯尔有限公司版权所有。
We evaluated the effects of agonists and antagonist of toll-like receptor (TLR) 9 in comparison with a TLR3 agonist in a mouse model of herpes simplex virus type 1 (HSV-1) encephalitis (HSE). BALB/c mice received a single intranasal dose of either a TLR3 agonist (polyinosinic:polycytidylic acid; PIC), TLR9 agonists (oligodeoxynucleotides (ODNs) 1585, 1826 or 2395) or a TLR9 antagonist (ODN 2088), 1 day before and, for selected groups, 3 days after infection with HSV-1. Mice that received the pre-treatment with vehicle, PIC, ODNs 1585, 1826, 2395 and 2088 before infection had survival rates of 25%, 65%, 55%, 40%, 55% and 30%, respectively (P < 0.05 for PIC and ODNs 1585 and 2395 versus vehicle). Infected mice subsequently treated with vehicle. ODNs 2395 and 2088 had survival rates of 9%, 0% and 30%, respectively (P < 0.05, ODN 2088 versus other groups). The pre-treatment of mice with ODN 2395 reduced both the viral load (P < 0.05 at day 5) and the production of CCL2, IL-6 and CCL5 at days 3, 4 and 5 (P < 0.05 for IL-6 at day 3 and P < 0.05 for CCL2 and CCL5 at day 4). Treatment of infected mice with ODN 2088 reduced the production of the same cytokines (P = 0.07 for CCL2 and P = 0.09 for IL-6 at day 5). Pre-treatment of mice with TLR9 agonists before infection reduces brain viral load and cytokine levels resulting in increased HSE survival rates. On the other hand, TLR9 antagonists can be helpful to control the inflammatory response that could be detrimental after infection. (C) 2012 Elsevier B.V. All rights reserved.