Bibliographic Details
| Title: |
VEGFR-3 signaling restrains the neuron-macrophage crosstalk during neurotropic viral infection |
| Authors: |
Linlin Qi, Xiaojing Li, Fang Zhang, Xingguo Zhu, Qi Zhao, Dan Yang, Shujie Hao, Tong Li, Xiangyue Li, Taikun Tian, Jian Feng, Xiaochen Sun, Xilin Wang, Shangyan Gao, Hanzhong Wang, Jing Ye, Shengbo Cao, Yulong He, Hongyan Wang, Bin Wei |
| Source: |
Cell Reports, Vol 42, Iss 5, Pp 112489- (2023) |
| Publisher Information: |
Elsevier, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
CP: Immunology, CP: Neuroscience, Biology (General), QH301-705.5 |
| More Details: |
Summary: Upon recognizing danger signals produced by virally infected neurons, macrophages in the central nervous system (CNS) secrete multiple inflammatory cytokines to accelerate neuron apoptosis. The understanding is limited about which key effectors regulate macrophage-neuron crosstalk upon infection. We have used neurotropic-virus-infected murine models to identify that vascular endothelial growth factor receptor 3 (VEGFR-3) is upregulated in the CNS macrophages and that virally infected neurons secrete the ligand VEGF-C. When cultured with VEGF-C-containing supernatants from virally infected neurons, VEGFR-3+ macrophages suppress tumor necrosis factor α (TNF-α) secretion to reduce neuron apoptosis. Vegfr-3ΔLBD/ΔLBD (deletion of ligand-binding domain in myeloid cells) mice or mice treated with the VEGFR-3 kinase inhibitor exacerbate the severity of encephalitis, TNF-α production, and neuron apoptosis post Japanese encephalitis virus (JEV) infection. Activating VEGFR-3 or blocking TNF-α can reduce encephalitis and neuronal damage upon JEV infection. Altogether, we show that the inducible VEGF-C/VEGFR-3 module generates protective crosstalk between neurons and macrophages to alleviate CNS viral infection. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124723005004; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112489 |
| Access URL: |
https://doaj.org/article/9b699b87a8064568a34d1937e6ff50ef |
| Accession Number: |
edsdoj.9b699b87a8064568a34d1937e6ff50ef |
| Database: |
Directory of Open Access Journals |
