The lymphatic system favours survival of a uniqueT. bruceipopulation, and its invasion results in major host pathology

Abstract

AbstractTrypanosoma bruceicolonize and multiply in the blood vasculature, as well as in various organs of the host’s body. Lymph nodes have been previously shown to harbour large numbers of parasites, and the lymphatic system has been proposed as a key site that allowsT. bruceidistribution through, and colonization of the mammalian body. However, visualization of host-pathogen interactions in the lymphatic system has never captured dynamic events with high spatial and temporal resolution throughout infection. In our work, we used a mixture of tools including intravital microscopy andex vivoimaging to studyT. bruceidistribution in 20 sets of lymph nodes. We demonstrate that lymph node colonization byT. bruceiis different across lymph node sets, with the most heavily colonized being the draining lymph nodes of main tissue reservoirs: the gonadal adipose tissue and pancreas. Moreover, we show that the lymphatic vasculature is a pivotal site for parasite dispersal, and altering this colonization by blocking LYVE-1 (i.e. surface receptor of lymphatic vessel endothelial cells) is detrimental for parasite survival. Additionally, parasites within the lymphatic vasculature have unique morphological and behavioural characteristics, different to those found in the blood, demonstrating a physical separation of environments across both types of vasculature. Finally, we demonstrate that the lymph nodes and the lymphatic vasculature undergoes significant alterations duringT. bruceiinfection, resulting in oedema throughout the host’s body.