A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP.
A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP.
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DOI：
10.1084/jem.20082874
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发表时间：
2009-08-31
期刊：
影响因子：
--
通讯作者：
Vance RE
中科院分区：
文献类型：
--
作者：
McWhirter SM;Barbalat R;Monroe KM;Fontana MF;Hyodo M;Joncker NT;Ishii KJ;Akira S;Colonna M;Chen ZJ;Fitzgerald KA;Hayakawa Y;Vance RE
先天免疫系统对独特的分子特征作出反应，这些分子特征在微生物中广泛保守，但通常不存在于宿主细胞中。刺激先天免疫途径的化合物在设计新型佐剂、疫苗和其他免疫治疗剂中可能是有价值的。环二核苷酸环二鸟苷一磷酸（c-di-GMP）是一种新近发现的第二信使，在许多细菌中起着重要的调节作用，但不是由真核细胞产生的。体内和体外研究表明，c-di-GMP是一种有效的免疫刺激化合物，可被小鼠和人类细胞识别。我们提供的证据表明，c-di-GMP是通过一种新的免疫监视途径在哺乳动物细胞的胞质溶胶中。由c-di-GMP诱导的胞质信号传导的效力与由DNA的胞质递送诱导的胞质信号传导的效力相当，并且两种核酸诱导相似的转录谱，包括通过诱导TBK 1、IRF 3、核因子κB和MAP激酶来触发I型干扰素和共调节基因。然而，感知c-di-GMP的胞质途径似乎与所有已知的核酸感知途径不同。我们的研究结果提示了一种新的机制，宿主细胞可以通过这种机制诱导对广泛产生的细菌配体的炎症反应。
The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid–sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand.
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细菌外多糖产生所需的环状-DI-GMP受体。
影响因子：
3.6
作者：
Lee, Vincent T;Matewish, Jody M;Kessler, Jennifer L;Hyodo, Mamoru;Hayakawa, Yoshihiro;Lory, Stephen
通讯作者：
Lory, Stephen
DOI：
10.1073/pnas.2237236100
发表时间：
2004-01-06
影响因子：
11.1
作者：
McWhirter, SM;Fitzgerald, KA;Maniatis, T
通讯作者：
Maniatis, T
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
I型干扰素信号在弗朗西斯拉感染过程中激活炎症体需要。
影响因子：
15.3
作者：
Henry, Thomas;Brotcke, Anna;Weiss, David S.;Thompson, Lucinda J.;Monack, Denise M.
通讯作者：
Monack, Denise M.
影响因子：
5.5
作者：
Ebensen, Thomas;Schulze, Kai;Guzman, Carlos A.
通讯作者：
Guzman, Carlos A.