Streptococcus pneumoniae (the pneumococcus) is one of the leading causes of death due to infectious disease in the world, with over one million deaths being attributed to this bacterium each year. While the majority of these deaths occur in children in developing nations, significant morbidity and mortality in the developed world, especially in the elderly, can be attributed to pneumococcal diseases such as bacterial pneumonia and meningitis. This is despite the near-universal use of anti-pneumococcal vaccines in these parts of the world. The work presented in this thesis describes the ways in which resident nasal macrophages respond to nasopharyngeal pneumococcal colonization, allowing for the protection of immunocompetent individuals from these diseases. This thesis describes the role of the macrophage scavenger receptor MARCO in recognizing the bacterium upon colonization, and the chain of events that are subsequently established. I have found that MARCO is vital in orchestrating the clearance of pneumococci from the nasopharynx in an expedient manner, as well as preventing the swift spread of bacteria to other tissues of the body early on in colonization. I also outline a role for regulatory micro-RNAs present in macrophages in the mounting of this anti-pneumococcal response via the induction of specific T cell populations. The collection of data found herein is an important resource for those attempting to understand the complex narrative that takes place between the pneumococcus and the innate immune system during a colonizing event and will lead to further discovery on how healthy individuals escape fatal pneumococcal disease. / Thesis / Doctor of Philosophy (PhD) / The bacterium Streptococcus pneumoniae is one of the most dangerous pathogens in the world, accounting for more one million deaths every year worldwide. This bacterium is also very common, with approximately one third of all people having some S. pneumoniae in their noses at any given time. The goal of this thesis is to provide a better understanding of how our immune cells interact with S. pneumoniae when it first enters our noses and how these initial interactions prevent healthy people from becoming sick. I have found that white blood cells called macrophages are crucial to these interactions. Macrophages are able to ‘eat’ the bacteria using a specialized protein called MARCO to grab onto them. This information will be vital in trying to develop new vaccines and treatments for S. pneumoniae-related diseases like bacterial pneumonia (lung infection) and meningitis (brain infection).
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/18659 |
| Date | January 2016 |
| Creators | Dorrington, Michael |
| Contributors | Bowdish, Dawn, Medical Sciences (Molecular Virology and Immunology Program) |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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