The lymphatic system favours survival of a unique T. brucei population

Abstract

Trypanosoma brucei colonize 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 allows T. brucei distribution 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 and ex vivo imaging to study T. brucei distribution in 20 sets of lymph nodes. We demonstrate that lymph node colonization by T. brucei is different across lymph node sets, with the most heavily colonized being the draining lymph nodes of main tissue reservoirs: the gonadal white 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 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 that across both types of vasculature, these environments are physically separated. Finally, we demonstrate that the lymph nodes and the lymphatic vasculature undergo significant alterations during T. brucei infection, resulting in oedema throughout the host's body.

Spatial confinement of Trypanosoma brucei in microfluidic traps provides a new tool to study free swimming parasites

“…This would allow us to study the effect of environment geometry as one of multiple components governing parasite single and collective behaviour. Several studies have focused on the different behaviour exhibited by T. brucei in anatomical locations of different geometry, both in different compartments of the tsetse fly [40][41][42], and different organs and compartments of the mammalian host [43][44][45]. Specifically, and relevant to our observations in Tryp-Chip, we found that parasite motility is affected both, by parasite density, and tissue geometry [46].…”

Consistent detection of Trypanosoma brucei but not T. congolense DNA in faeces of experimentally-infected cattle

“…For T. brucei, the intestinal lumen presents the most obvious point of entry into the faeces. T. brucei has previously been recorded in extravascular lymphoid and adipose tissue surrounding the gastrointestinal tract (GIT) in mice 37,38 , and in peritoneal fluid of infected sheep 40 -however, there was no evidence of extravascular T. congolense in similar infection studies in rats 41 . To what extent T. brucei invades GIT mucosal or epithelial tissue, or sequesters in gut-associated lymphoid tissue within the intestines, is not certain.…”

“…GIT pathology findings in T. b. brucei experimentally-infected mice have included villus atrophy and oedema of the lamina propria as a result of inflammation 34,35 . Although extravascular T. brucei parasites have been found in the peritoneal fluid of experimentally-infected cattle 36 and the adipose tissue and lymph nodes surrounding the mesentery of infected mice 37,38 , T. brucei has not been recorded in the GIT mucosa or lumen. In contrast, we are not aware of any evidence of T. congolense in these locations.…”