Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis

被引：82

作者：

Chhatbar, Chintan ^{[1
,2
]}

Detje, Claudia N. ^{[1
,2
]}

Grabski, Elena ^{[1
,2
,11
]}

Borst, Katharina ^{[1
,2
,4
]}

Spanier, Julia ^{[1
,2
]}

Ghita, Luca ^{[1
,2
]}

Elliott, David A. ^{[3
,12
]}

Jordao, Marta Joana Costa ^{[4
,5
]}

Mueller, Nora ^{[6
]}

Sutton, James ^{[7
,13
]}

Prajeeth, Chittappen K. ^{[8
]}

Gudi, Viktoria ^{[8
]}

Klein, Michael A. ^{[6
]}

Prinz, Marco ^{[4
,9
]}

Bradke, Frank ^{[3
]}

Stangel, Martin ^{[8
,10
]}

Kalinke, Ulrich ^{[1
,2
,10
]}

机构：

[1] Helmholtz Ctr Infect Res, Inst Expt Infect Res, TWINCORE, Ctr Expt & Clin Infect Res,Joint Venture Helmholt, Hannover, Germany

[2] Hannover Med Sch, Hannover, Germany

[3] German Ctr Neurodegenerat Dis Res DZNE, Axonal Growth & Regenerat Grp, Bonn, Germany

[4] Freiburg Univ, Med Ctr, Inst Neuropathol, Freiburg, Germany

[5] Univ Freiburg, Fac Biol, Freiburg, Germany

[6] Univ Wurzburg, Inst Virol & Immunobiol, Wurzburg, Germany

[7] Novartis Inst Biomed Res, Emeryville, CA USA

[8] Hannover Med Sch, Dept Neurol, Clin Neuroimmunol & Neurochem, Hannover, Germany

[9] Univ Freiburg, BIOSS Ctr Biol Signaling Studies, Freiburg, Germany

[10] Ctr Syst Neurosci, Hannover, Germany

[11] Fed Inst Vaccines & Biomed, Paul Ehrlich Inst, Sect Viral Vaccines, Div Virol, Langen, Germany

[12] Univ Calgary, Hotchkiss Brain Inst Adv Microscopy Platform, Calgary, AB T2N 4N1, Canada

[13] IDEAYA Biosci Inc, 2200 Sand Hill Rd,Suite 110, Menlo Pk, CA 94025 USA

来源：

CELL REPORTS | 2018年 / 25卷 / 01期

关键词：

CENTRAL-NERVOUS-SYSTEM; VESICULAR STOMATITIS; MYELOID CELLS; BRAIN; INFECTIONS; MONOCYTES; DISTINCT; GENE; REPLICATION; MACROPHAGES;

D O I：

10.1016/j.celrep.2018.09.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

In sterile neuroinflammation, a pathological role is proposed for microglia, whereas in viral encephalitis, their function is not entirely clear. Many viruses exploit the odorant system and enter the CNS via the olfactory bulb (OB). Upon intranasal vesicular stomatitis virus instillation, we show an accumulation of activated microglia and monocytes in the OB. Depletion of microglia during encephalitis results in enhanced virus spread and increased lethality. Activation, proliferation, and accumulation of microglia are regulated by type I IFN receptor signaling of neurons and astrocytes, but not of microglia. Morphological analysis of myeloid cells shows that type I IFN receptor signaling of neurons has a stronger impact on the activation of myeloid cells than of astrocytes. Thus, in the infected CNS, the cross talk among neurons, astrocytes, and microglia is critical for full microglia activation and protection from lethal encephalitis.

引用

页码：118 / +

页数：16

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