The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Infection

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Visceral leishmaniasis (VL), a globally important parasitic disease responsible for over 40,000 deaths p.a., results in pronounced changes in splenic organisation associated with impaired immune function and persistent parasite infection. We have previously shown that receptor tyrosine kinase (RTKi) inhibitors can restore splenic architecture and improve immunocompetence, and that mononuclear phagocytes (MPs) are involved in this process. Here, we provide evidence that neurotrophin receptor Ntrk2 (also known as TrkB) plays a role in the pathologic remodeling of the spleen that accompanies experimental Leishmania donovani-infection. We show that following infection of mice with L.donovani, Ntrk2 is expressed on splenic endothelial cells that are closely associated with F4/80hiCD11bloCD11c+ macrophages expressing Ntrk2 ligands. Administration of the Ntrk2 antagonist ANA-12 to infected mice significantly inhibited compartment-specific vascular remodeling of the spleen. This study expands our understanding of the pathogenesis of experimental VL and also demonstrates the potential of Ntrk2/Bdnf as targets for treatment of infection-induced vascular remodeling.

Vyšlo v časopise: The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Infection. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004681
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004681

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