MyD88 signaling by neurons induces chemokines that recruit protective leukocytes to the virus-infected CNS.
MyD88 signaling by neurons induces chemokines that recruit protective leukocytes to the virus-infected CNS.
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DOI：
10.1126/sciimmunol.abc9165
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发表时间：
2021-06-25
影响因子：
24.8
通讯作者：
Kalinke U
中科院分区：
文献类型：
--
作者：
Ghita L;Spanier J;Chhatbar C;Mulenge F;Pavlou A;Larsen PK;Waltl I;Lueder Y;Kohls M;Jung K;Best SM;Förster R;Stangel M;Schreiner D;Kalinke U
病毒性脑炎在大脑中引发一系列免疫事件，可导致脑损伤和死亡。星形胶质细胞对嗜神经性感染做出反应，表达IFN-β，而活化的小胶质细胞产生促炎细胞因子并在感染部位积聚。在这里，我们观察到嗜神经性水泡性口炎病毒（VSV）感染导致白细胞募集到中枢神经系统（CNS），这需要MyD 88，Toll样受体和白细胞介素-1受体信号转导的适配器。浸润的白细胞，特别是CD 8 + T细胞，保护CNS免受致死性VSV感染。MyD 88在神经元中的重建恢复了嗅球中趋化因子的产生以及白细胞招募到感染的CNS中并提高了存活率。对神经元和星形胶质细胞的翻译组的比较分析证实神经元是趋化因子的关键来源，其调节受感染脑的白细胞浸润并影响存活。在病毒CNS感染期间，受感染神经元中的MyD 88信号传导协调保护性外周免疫细胞的募集。
Viral encephalitis initiates a series of immunological events in the brain that can lead to brain damage and death. Astrocytes express IFN-β in response to neurotropic infection, whereas activated microglia produce proinflammatory cytokines and accumulate at sites of infection. Here, we observed that neurotropic vesicular stomatitis virus (VSV) infection causes recruitment of leukocytes into the central nervous system (CNS), which requires MyD88, an adaptor of Toll-like receptor and interleukin-1 receptor signaling. Infiltrating leukocytes, and in particular CD8+ T cells, protected against lethal VSV infection of the CNS. Reconstitution of MyD88 specifically in neurons restored chemokine production in the olfactory bulb as well as leukocyte recruitment into the infected CNS and enhanced survival. Comparative analysis of the translatome of neurons and astrocytes verified neurons as the critical source of chemokines, which regulated leukocyte infiltration of the infected brain and impacted survival. During viral CNS infection, MyD88-signaling in infected neurons orchestrates recruitment of protective peripheral immune cells.
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影响因子：
3.8
作者：
Hoffmann, Markus;Wu, Yuan-Ju;Zimmer, Gert
通讯作者：
Zimmer, Gert
影响因子：
4.8
作者：
Bookstaver PB;Mohorn PL;Shah A;Tesh LD;Quidley AM;Kothari R;Bland CM;Weissman S
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作者：
Garber, Charise;Soung, Allison;Klein, Robyn S.
通讯作者：
Klein, Robyn S.
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通讯作者：
Klein RS
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Hosking MP;Lane TE
通讯作者：
Lane TE