| First Author | Qi L | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 5 | Pages | 112489 |
| PubMed ID | 37167063 | Mgi Jnum | J:348573 |
| Mgi Id | MGI:7491442 | Doi | 10.1016/j.celrep.2023.112489 |
| Citation | Qi L, et al. (2023) VEGFR-3 signaling restrains the neuron-macrophage crosstalk during neurotropic viral infection. Cell Rep 42(5):112489 |
| abstractText | 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 alpha (TNF-alpha) secretion to reduce neuron apoptosis. Vegfr-3(DeltaLBD/DeltaLBD) (deletion of ligand-binding domain in myeloid cells) mice or mice treated with the VEGFR-3 kinase inhibitor exacerbate the severity of encephalitis, TNF-alpha production, and neuron apoptosis post Japanese encephalitis virus (JEV) infection. Activating VEGFR-3 or blocking TNF-alpha 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. |
