Thesis
Metabolic reprogramming of dendritic cells by intracellular protozoan parasites
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2018
- Thesis identifier
- T15217
- Person Identifier (Local)
- 201473133
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Upon activation, immune cells such as macrophages and dendritic cells alter their metabolism to support phagocytosis, antigen processing, cytokine production and T cell activation. Even in an oxygenated environment, immune cells change their metabolism from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. This is referred to as the ‘Warburg effect’. Aerobic glycolysis benefits the immune response by rapidly generating ATP whilst disruption of OXPHOS results in accumulation of intermediate metabolites which are used for other immunological purposes. The situation is further complicated by intracellular pathogens that compete for host resources or even manipulate metabolic pathways for their own gain. To combat this, hosts have evolved mechanisms to restrict the availability of certain metabolites to suppress pathogen growth. The following studies were undertaken to determine the interplay between DCs and Leishmania and Toxoplasma. A polyomics approach comprising of transcriptomic and metabolic analyses validated with functional assays was employed to investigate the effect of L. mexicana or T. gondii on the BMDC phenotype. The data observes transcript and metabolic changes including aerobic glycolysis and reduced oxidative phosphorylation demonstrating the Warburg effect. Consistent with this, LDH activity was upregulated and mitochondrial membrane potential reduced in L. mexicana and T. gondii infected BMDC cultures. In addition, certain changes to BMDC metabolism would appear to be parasite evolved to promote their growth and survival. In L. mexicana infected BMDCs, accumulation of itaconate (a TCA intermediate) could be associated with the reduction of pro-inflammatory cytokine production. Furthermore, changes in arginine metabolism including upregulation of arginase, ornithine and proline production were observed in T. gondii infected BMDCs and are likely to reflect the coevolution of parasite and host. These results highlight the complex interplay of host and parasite metabolism with the developing immune response in BMDCs.
- Advisor / supervisor
- Roberts, Craig
- Resource Type
- Note
- This thesis was previously held under moratorium from 11th September 2019 until 11th September 2024.
- DOI
- Date Created
- 2018
- Former identifier
- 9912723193002996
关系
项目
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PDF of thesis T15217 | 2021-07-02 | 公开 | 下载 |