| First Author | Dalton JE | Year | 2015 |
| Journal | PLoS Pathog | Volume | 11 |
| Issue | 2 | Pages | e1004681 |
| PubMed ID | 25710496 | Mgi Jnum | J:246217 |
| Mgi Id | MGI:5918531 | Doi | 10.1371/journal.ppat.1004681 |
| Citation | Dalton JE, et al. (2015) The neurotrophic receptor Ntrk2 directs lymphoid tissue neovascularization during Leishmania donovani infection. PLoS Pathog 11(2):e1004681 |
| abstractText | The neurotrophic tyrosine kinase receptor type 2 (Ntrk2, also known as TrkB) and its ligands brain derived neurotrophic factor (Bdnf), neurotrophin-4 (NT-4/5), and neurotrophin-3 (NT-3) are known primarily for their multiple effects on neuronal differentiation and survival. Here, we provide evidence that Ntrk2 plays a role in the pathologic remodeling of the spleen that accompanies chronic infection. We show that in Leishmania donovani-infected mice, Ntrk2 is aberrantly expressed on splenic endothelial cells and that new maturing blood vessels within the white pulp are intimately associated with F4/80(hi)CD11b(lo)CD11c(+) macrophages that express Bdnf and NT-4/5 and have pro-angiogenic potential in vitro. Furthermore, administration of the small molecule Ntrk2 antagonist ANA-12 to infected mice significantly inhibited white pulp neovascularization but had no effect on red pulp vascular remodeling. We believe this to be the first evidence of the Ntrk2/neurotrophin pathway driving pathogen-induced vascular remodeling in lymphoid tissue. These studies highlight the therapeutic potential of modulating this pathway to inhibit pathological angiogenesis. |
