Trypanosoma carassii is an extracellular blood parasite of cyprinid fish phylogenetically closely related to Trypanosoma brucei, the causative agent of the sleeping sickness disease in humans and livestock. Motility is crucial for trypanosome pathogenicity, but real-time visualization of parasite movement in vivo, in the natural host environment, has not been reported thus far. In this study, we report the establishment of T. carassii infection in zebrafish (Danio rerio), which allowed us, for the first time in a vertebrate host, to characterize in details the movement of trypanosomes in vivo. By combining the transparency of zebrafish larvae with the availability of several transgenic lines marking macrophages, neutrophils, cytokine-expressing leukocytes and endothelial cells, we were able to study in real-time: 1) parasite movement in vivo; 2) the kinetics of innate immune responses; and 3) parasite interaction with host (immune) cells. Our results indicate that during T. carassii infection of young zebrafish a differential macrophages and neutrophils response is observed. Macrophages responded more prominently than neutrophils by proliferating, and were massively recruited to blood vessels. Macrophages also exhibited heterogeneous morphologies and a strong pro-inflammatory profile. In fact, they were strongly positive for Tnfα and Il-1β and had a morphology characteristic of foamy macrophages. Large foamy macrophages accumulated in the portal vein of highly infected individuals, and were strongly positive for lipid staining, which revealed the abundance of lipid bodies in their cytoplasm. Finally, with respect to parasite movement and interaction with the host, using high-speed videography, we were able to capture novel mechanisms of parasite-host cell interaction, and to follow the onset of anemia, vasodilation and extravasation typical of trypanosome infections. Altogether, this is the first report of an in vivo trypanosome infection model in a natural vertebrate host describing both, the pathogen behavior and the host response. Considering that trypanosomes can infect all vertebrates, including humans, livestock and fish, our infection model is a relevant complementary tool to gain more insights in the underlying mechanisms of trypanosome infections.
|Number of pages||1|
|Journal||Fish and Shellfish Immunology|
|Publication status||Published - 2019|
|Event||International Fish & Shellfish Immunology Congress 2019 - Gran Canaria, Spain|
Duration: 16 Jun 2019 → 20 Jun 2019