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http://hdl.handle.net/11375/20474
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DC Field | Value | Language |
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dc.contributor.advisor | Bowdish, Dawn | - |
dc.contributor.author | Naidoo, Aveshni | - |
dc.date.accessioned | 2016-09-23T19:27:55Z | - |
dc.date.available | 2016-09-23T19:27:55Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://hdl.handle.net/11375/20474 | - |
dc.description.abstract | Aging is accompanied by increasing levels of pro-inflammatory cytokines, such as tumour necrosis factor (TNF), in the serum and tissues and changes in the phenotype and function of leukocytes. This “inflamm-aging” is known to contribute to numerous chronic diseases associated with aging and an increased susceptibility to infection. We hypothesized that age-associated increases in pro-inflammatory cytokines, TNF, contribute to monocyte and macrophage dysfunction, and ultimately, and an increased susceptibility to disease in the elderly and those with chronic inflammation. In this thesis, we conclude that TNF is a key mediator of age-associated inflammation, contributes to changes in inflammatory monocyte development, phenotype and function, and ultimately, impaired anti-pneumococcal immunity. We found that age-associated impairments in monocyte and macrophage function were influenced by the age of the host microenvironment, and not hematopoietic stem cells. Remarkably, exposure of aged immune cells to the microenvironment of a young host could reverse the detrimental effects of age and rescue monocyte and macrophage function. Moreover, in a model of diet-induced obesity, we demonstrated that inflammatory monocyte characteristics, which are regulated by TNF, could serve as a better predictor of insulin resistance in mice and humans than conventional biomarkers. Lastly, we demonstrate that TNF drives age-related defects in muscle function and mobility with age. Together, these studies increase the breadth of our understanding of the cross talk between inflammatory micro-environment and host immunity, and their impact on age-associated diseases. Although there are many more details to be unraveled, these studies indeed have made great progress and could be used to develop novel and much-needed therapeutic strategies to reduce the risk of infectious and chronic disease and improve the quality of life in the aging population. | en_US |
dc.language.iso | en | en_US |
dc.title | TNF Alters Monocyte and Macrophage Phenotype and Function in Models of Chronic Inflammatory Disease | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Medical Sciences (Molecular Virology and Immunology Program) | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Naidoo_Aveshni_finalsubmission2016august_degree.pdf | 54.63 MB | Adobe PDF | View/Open |
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