Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans.
Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans.
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DOI：
10.1084/jem.20111171
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发表时间：
2011-11-21
期刊：
影响因子：
--
通讯作者：
Sékaly RP
中科院分区：
文献类型：
--
作者：
Caskey M;Lefebvre F;Filali-Mouhim A;Cameron MJ;Goulet JP;Haddad EK;Breton G;Trumpfheller C;Pollak S;Shimeliovich I;Duque-Alarcon A;Pan L;Nelkenbaum A;Salazar AM;Schlesinger SJ;Steinman RM;Sékaly RP
通过对人类志愿者血液样本的转录分析显示，注射合成的dsRNA （TLR3和MDA5模式识别受体的激动剂）触发了先天免疫途径相关基因的上调，类似于接种有效的黄热病疫苗所诱导的上调。佐剂对疫苗的成功至关重要。微生物模式识别受体（PRRs）激动剂是一种很有前途的新型佐剂。佐剂增强免疫应答的一种机制是刺激先天免疫。我们研究了人类对合成双链RNA（聚肌苷：聚赖氨酸稳定的多胞酸[poly IC]）、toll样受体（TLR） 3的激动剂和细胞质RNA解旋酶MDA-5)的先天免疫反应。对8名志愿者皮下注射poly ICLC后的血液样本进行转录分析，结果显示所有受试者参与多种先天免疫途径的基因均上调，包括干扰素（IFN）和炎性体信号传导。体外阻断I型IFN受体显著抑制了对poly IC的应答。比较转录分析显示，在接种高效黄热病疫苗的志愿者中，几种先天免疫途径被类似地诱导。因此，化学上定义的PRR激动剂，如聚ICLC，可以是一种可靠的、真实的微生物模拟物，用于诱导人类的先天免疫反应。
As shown by transcriptional analysis of blood samples from human volunteers, injection with synthetic dsRNA (an agonist of the TLR3 and MDA5 pattern recognition receptors) triggered up-regulation of genes involved in innate immune pathways, similar to those induced by vaccination with the efficacious yellow fever vaccine. Adjuvants are critical for the success of vaccines. Agonists of microbial pattern recognition receptors (PRRs) are promising new adjuvant candidates. A mechanism through which adjuvants enhance immune responses is to stimulate innate immunity. We studied the innate immune response in humans to synthetic double-stranded RNA (polyinosinic:polycytidylic acid [poly IC] stabilized with poly-l-lysine [poly ICLC]), an agonist for toll-like receptor (TLR) 3, and the cytosolic RNA helicase MDA-5. Transcriptional analysis of blood samples from eight volunteers, after subcutaneous administration of poly ICLC, showed up-regulation of genes involved in multiple innate immune pathways in all subjects, including interferon (IFN) and inflammasome signaling. Blocking type I IFN receptor ex vivo significantly dampened the response to poly IC. Comparative transcriptional analysis showed that several innate immune pathways were similarly induced in volunteers immunized with the highly efficacious yellow fever vaccine. Therefore, a chemically defined PRR agonist like poly ICLC can be a reliable and authentic microbial mimic for inducing innate immune responses in humans.
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DOI：
10.1126/science.1179050
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amit I;Garber M;Chevrier N;Leite AP;Donner Y;Eisenhaure T;Guttman M;Grenier JK;Li W;Zuk O;Schubert LA;Birditt B;Shay T;Goren A;Zhang X;Smith Z;Deering R;McDonald RC;Cabili M;Bernstein BE;Rinn JL;Meissner A;Root DE;Hacohen N;Regev A
通讯作者：
Regev A
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
11.8
作者：
Plotkin, Stanley A.
通讯作者：
Plotkin, Stanley A.
影响因子：
5.4
作者：
Harris, James;Sharp, Fiona A.;Lavelle, Ed C.
通讯作者：
Lavelle, Ed C.