TY  - JOUR
AU  - Dalton, JE
AU  - Glover, AC
AU  - Hoodless, L
AU  - Lim, E-K
AU  - Beattie, L
AU  - Kirby, A
AU  - Kaye, PM
Y2  - 2020/12/18
Y1  - 2015/02/01
SN  - 1553-7366
UR  - http://hdl.handle.net/11343/255851
AB  - 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.
LA  - English
PB  - PUBLIC LIBRARY SCIENCE
T1  - The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Leishmania donovani Infection
DO  - 10.1371/journal.ppat.1004681
IS  - PLoS Pathogens
VL  - 11
IS  - 2
L1  - /bitstream/handle/11343/255851/PMC4339582.pdf?sequence=1&isAllowed=y
ER  -