Herpes Simplex Virus Type 1 Engages Toll Like Receptor 2 to Recruit Macrophages During Infection of Enteric Neurons.
Herpes Simplex Virus Type 1 Engages Toll Like Receptor 2 to Recruit Macrophages During Infection of Enteric Neurons.
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DOI：
10.3389/fmicb.2018.02148
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发表时间：
2018
影响因子：
5.2
通讯作者：
Castagliuolo I
中科院分区：
文献类型：
--
作者：
Brun P;Scarpa M;Marchiori C;Conti J;Kotsafti A;Porzionato A;De Caro R;Scarpa M;Calistri A;Castagliuolo I
单纯疱疹病毒1型（HSV-1）是一种广泛分布的嗜神经性病原体，可引起一系列临床表现。炎性细胞浸润是HSV-1感染的常见特征，并与神经变性有关。因此，先天免疫受体（即，TLR 2）和随后的炎症反应现在被认为是HSV-1发病机制中的关键参与者。本研究用HSV-1感染野生型（WT）和TLR 2基因敲除（TLR 2ko）小鼠的肠神经系统（ENS），以研究TLR 2是否以及如何参与HSV-1诱导的神经肌肉功能障碍。我们的研究结果表明，病毒特异性转录本提示在WT和TLR 2ko小鼠的ENS中复制失败。此外，HSV-1触发TLR 2-MyD 88依赖性信号在肌间神经元和诱导的结构和功能的变化的ENS。然而，胃肠道动力障碍是不太明显的TLR 2ko相比，WT小鼠。有趣的是，HSV-1引起WT小鼠肌间神经节中单核细胞趋化蛋白-1（CCL 2）的上调和CD 11b+巨噬细胞的募集，而不是TLR 2ko小鼠。相反，TLR 2ko小鼠的肌间神经丛被HSV-1反应性CD 3 + CD 8 +INFγ+淋巴细胞的密集浸润包围。事实上，通过施用抗CD 8单克隆抗体来消耗CD 3 + CD 8+细胞减少了感染HSV-1的TLR 2ko小鼠的神经肌肉功能障碍。在HSV-1感染期间，TLR 2的参与介导受感染神经元中CCL 2的产生并协调巨噬细胞募集。考虑到这些观察结果，TLR 2信号传导的阻断可以提供新的治疗策略，以支持保护性和特异性T细胞应答，并改善病原体介导的ENS改变中的神经肌肉功能障碍。
Herpes simplex virus type 1 (HSV-1) is a widespread neurotropic pathogen responsible for a range of clinical manifestations. Inflammatory cell infiltrate is a common feature of HSV-1 infections and has been implicated in neurodegeneration. Therefore, viral recognition by innate immune receptors (i.e., TLR2) and the subsequent inflammatory response are now deemed key players in HSV-1 pathogenesis. In this study we infected with HSV-1 the enteric nervous system (ENS) of wild-type (WT) and TLR2 knock-out (TLR2ko) mice to investigate whether and how TLR2 participates in HSV-1 induced neuromuscular dysfunction. Our findings demonstrated viral specific transcripts suggestive of abortive replication in the ENS of both WT and TLR2ko mice. Moreover, HSV-1 triggered TLR2-MyD88 depend signaling in myenteric neurons and induced structural and functional alterations of the ENS. Gastrointestinal dysmotility was, however, less pronounced in TLR2ko as compared with WT mice. Interesting, HSV-1 caused up-regulation of monocyte chemoattractant protein-1 (CCL2) and recruitment of CD11b+ macrophages in the myenteric ganglia of WT but not TLR2ko mice. At the opposite, the myenteric plexuses of TLR2ko mice were surrounded by a dense infiltration of HSV-1 reactive CD3+CD8+INFγ+ lymphocytes. Indeed, depletion CD3+CD8+ cells by means of administration of anti-CD8 monoclonal antibody reduced neuromuscular dysfunction in TLR2ko mice infected with HSV-1. During HSV-1 infection, the engagement of TLR2 mediates production of CCL2 in infected neurons and coordinates macrophage recruitment. Bearing in mind these observations, blockage of TLR2 signaling could provide novel therapeutic strategies to support protective and specific T-cell responses and to improve neuromuscular dysfunction in pathogen-mediated alterations of the ENS.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
8.3
作者：
GARCIA, JH;WAGNER, S;HU, XJ
通讯作者：
HU, XJ
DOI：
10.1126/science.1183021
发表时间：
2010-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iwasaki A;Medzhitov R
通讯作者：
Medzhitov R
影响因子：
64.5
作者：
Gabanyi I;Muller PA;Feighery L;Oliveira TY;Costa-Pinto FA;Mucida D
通讯作者：
Mucida D
影响因子：
3.4
作者：
Boivin, G;Coulombe, Z;Rivest, S
通讯作者：
Rivest, S