Understanding the tropism, immunology and pathology of African trypanosomiasis

Barnes, Chloe and Urbaniak, Mick and Worthington, John and Jackson-Jones, Lucy (2025) Understanding the tropism, immunology and pathology of African trypanosomiasis. PhD thesis, Lancaster University.

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Abstract

Trypanosoma brucei is a protozoan parasite that causes the neglected tropical disease African sleeping sickness. T. brucei can survive and develop a chronic infection in the mammalian host despite eliciting a strong anti-trypanosome immune response. The most severe infection symptoms are associated with the late-stage infection and parasite colonisation of the brain. However, parasite tissue niches in early infection are increasingly appreciated to have clinical importance particularly those in the skin and adipose tissue. A bioluminescent in vivo model of African trypanosomiasis was used to observe tissue tropism during infection. T. brucei parasites were identified at a high burden in the GI tract, a novel niche for this parasite. Analysis of the large intestine showed barrier inflammation with increased crypt pathology in histological staining of infected sections. I observed changes in immune cell populations of the large intestine lamina propria and gut-draining mesenteric lymph nodes along with alterations to host gene expression in the large intestine shown by bulk RNA sequencing. These results demonstrate a potential mechanism associated with brain pathology via the gut-brain axis. Adipose tissue loss is widely reported in experimental African trypanosomiasis, with weight loss and cachexia also observed in patients and cattle respectively. In this thesis the immune adipose tissues are studied, with lipid uptake by immune cells observed within fat-associated lymphoid clusters and a potential uptake mechanism proposed. High fat diet feeding during infection demonstrated a reduced parasite burden and protection of the host, suggesting that lipids acquired by immune cells during infection may be utilised to fuel the anti-trypanosome immune response to benefit the host.