The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Leishmania donovani Infection
AuthorDalton, JE; Glover, AC; Hoodless, L; Lim, E-K; Beattie, L; Kirby, A; Kaye, PM
Source TitlePLoS Pathogens
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sBeattie, Lynette
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsDalton, J. E., Glover, A. C., Hoodless, L., Lim, E. -K., Beattie, L., Kirby, A. & Kaye, P. M. (2015). The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Leishmania donovani Infection. PLOS PATHOGENS, 11 (2), https://doi.org/10.1371/journal.ppat.1004681.
Access StatusOpen Access
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.
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