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dc.contributor.authorDalton, JE
dc.contributor.authorGlover, AC
dc.contributor.authorHoodless, L
dc.contributor.authorLim, E-K
dc.contributor.authorBeattie, L
dc.contributor.authorKirby, A
dc.contributor.authorKaye, PM
dc.date.accessioned2020-12-18T03:37:46Z
dc.date.available2020-12-18T03:37:46Z
dc.date.issued2015-02-01
dc.identifierpii: PPATHOGENS-D-14-01842
dc.identifier.citationDalton, 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.
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/11343/255851
dc.description.abstractThe 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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleThe Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Leishmania donovani Infection
dc.typeJournal Article
dc.identifier.doi10.1371/journal.ppat.1004681
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titlePLoS Pathogens
melbourne.source.volume11
melbourne.source.issue2
dc.rights.licenseCC BY
melbourne.elementsid1312272
melbourne.contributor.authorBeattie, Lynette
dc.identifier.eissn1553-7374
melbourne.accessrightsOpen Access


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