Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota.
Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota.
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DOI：
10.1016/j.cell.2021.05.020
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发表时间：
2021-07-08
期刊：
影响因子：
64.5
通讯作者：
Belkaid Y
中科院分区：
文献类型：
--
作者：
Lima-Junior DS;Krishnamurthy SR;Bouladoux N;Collins N;Han SJ;Chen EY;Constantinides MG;Link VM;Lim AI;Enamorado M;Cataisson C;Gil L;Rao I;Farley TK;Koroleva G;Attig J;Yuspa SH;Fischbach MA;Kassiotis G;Belkaid Y
微生物群在调节宿主免疫中起着重要作用。然而，参与启动和调节对微生物群的免疫的过程在很大程度上仍然未知。在这里，我们表明，皮肤微生物群促进定义的内源性逆转录病毒（ERVs）的离散表达。ERV诱导的角质形成细胞内源性反应依赖于环GMP-AMP合酶（cGAS）/干扰素基因蛋白刺激因子（STING）信号通路，并促进了表皮特异性T细胞的诱导。ERV逆转录的抑制显著影响了这些反应，导致对微生物群及其相关组织修复功能的免疫力受损。相反，富含脂质的饮食引发皮肤响应于肠道定植而提高ERV表达，导致免疫应答和组织炎症增加。总之，我们的研究结果支持这样的观点，即宿主可能已经选择了其内源性病毒组作为与外源性微生物群交流的手段，从而导致控制组织稳态和炎症的多王国对话。内源性逆转录病毒传感是微生物群特异性免疫所需的逆转录抑制损害皮肤中的微生物群诱导的免疫角质形成细胞中的cGAS/STING信号传导是皮肤对微生物群的免疫所需的增强的内源性逆转录病毒表达促进微生物群诱导的炎症宿主免疫系统使用内源性病毒组与外源性微生物群在调节组织修复或炎症的多界相互作用中通信。
The microbiota plays a fundamental role in regulating host immunity. However, the processes involved in the initiation and regulation of immunity to the microbiota remain largely unknown. Here, we show that the skin microbiota promotes the discrete expression of defined endogenous retroviruses (ERVs). Keratinocyte-intrinsic responses to ERVs depended on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes protein (STING) signaling and promoted the induction of commensal-specific T cells. Inhibition of ERV reverse transcription significantly impacted these responses, resulting in impaired immunity to the microbiota and its associated tissue repair function. Conversely, a lipid-enriched diet primed the skin for heightened ERV- expression in response to commensal colonization, leading to increased immune responses and tissue inflammation. Together, our results support the idea that the host may have co-opted its endogenous virome as a means to communicate with the exogenous microbiota, resulting in a multi-kingdom dialog that controls both tissue homeostasis and inflammation. Endogenous retrovirus sensing is required for commensal-specific immunity Reverse transcription inhibition impairs commensal-induced immunity in the skin cGAS/STING signaling in keratinocytes is required for skin immunity to the microbiota Enhanced endogenous retrovirus expression promotes microbiota-induced inflammation The host immune system uses the endogenous virome to communicate with the exogenous microbiota in a multi-kingdom interaction that modulates tissue repair or inflammation.
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影响因子：
5.4
作者：
EVANS, LH;MORRISON, RP;BRITT, WJ
通讯作者：
BRITT, WJ
SAMHD1 通过促进应力颗粒形成来抑制 LINE-1 逆转座。
影响因子：
4.5
作者：
Hu S;Li J;Xu F;Mei S;Le Duff Y;Yin L;Pang X;Cen S;Jin Q;Liang C;Guo F
通讯作者：
Guo F
DOI：
10.1126/science.aax6624
发表时间：
2019-10-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Constantinides MG;Link VM;Tamoutounour S;Wong AC;Perez-Chaparro PJ;Han SJ;Chen YE;Li K;Farhat S;Weckel A;Krishnamurthy SR;Vujkovic-Cvijin I;Linehan JL;Bouladoux N;Merrill ED;Roy S;Cua DJ;Adams EJ;Bhandoola A;Scharschmidt TC;Aubé J;Fischbach MA;Belkaid Y
通讯作者：
Belkaid Y
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
5.4
作者：
Denton, Paul W.;Olesen, Rikke;Garcia, J. Victor
通讯作者：
Garcia, J. Victor