Thesis
Sex-influenced histopathological changes and the immunity during Toxoplasma gondii infection
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2020
- Thesis identifier
- T15543
- Person Identifier (Local)
- 201666581
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Studies indicate female mice are more susceptible to T. gondii infection in comparison to male mice. The following studies were undertaken to enhance our understanding about the influence of sex in the immune response during T. gondii infection and the disease outcome in BALB/c mice. Early parasite replication and immunological events were studied in parallel through applying an in vivo imaging system (IVIS) with luciferase expressing T. gondii and a cytometric bead array to quantify key immunological mediators. The results confirmed female mice to be more susceptible to acute infection, as determined by higher mortality rates and weight loss compared with males. However, conflicting with expectations female mice had lower parasite burdens during the acute infection than male mice. Female mice also exhibited a significantly increased production of MCP-1, IFN-y and TNF-a than male mice. These results suggest that a stronger immune response in females results in better parasite control, but has detrimental effects on health and mortality. Brain tissue of male and female mice chronically infected with T. gondii cysts were compared by using histopathological examination and RNAseq technologies to determine transcriptomic changes. The data indicate that female mice had increased pathology and developed more tissue cysts. The transcript analysis indicate that infected females had increased transcript levels of genes associated with PI3K/AKT/mTOR pathway, T cell exhaustion and apoptosis/pyroptosis. Consistent with these observations, female mice developed greater levels of DNA fragmentation as determined by TUNNEL and increased expression of NLRP3 in their brains. Overall, the results suggest that female mice mount a stronger immune response that controls parasite levels, but causes increased weight loss and mortality. In addition, the increased inflammation in the early stages of infection might account for the increased markers of T cell exhaustion that correlates with increased pathology in brains of female mice during T. gondii chronic stage.
- Advisor / supervisor
- Roberts, Craig
- Resource Type
- Note
- This thesis was previously held under moratorium from 8th April 2020 until 8th April 2022
- DOI
- Date Created
- 2020
- Former identifier
- 9912812689702996
Relations
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PDF of thesis T15543 | 2021-07-02 | Public | Download |