Harnessing Innate Immune Memory and Trained Innate Immunity Against Bacterial and Viral Infections
| dc.contributor.advisor | Xing, Zhou | |
| dc.contributor.author | Kang, Alisha | |
| dc.contributor.department | Medicine | en_US |
| dc.date.accessioned | 2025-09-22T14:00:22Z | |
| dc.date.available | 2025-09-22T14:00:22Z | |
| dc.date.issued | 2025 | |
| dc.description.abstract | In recent years, the ability to harness innate immune memory as a strategy to provide broad nonspecific protection against various pathogens has gained significant attention. Recent evidence indicates that systemic and more recently local immunological exposure to immune stimuli leads to alterations in the innate immune cell compartment, specifically tissue-resident macrophages at mucosal sites. Such alterations within the innate immune cell compartment can result in a strengthened immune response leading to enhanced innate immune protection or trained innate immunity (TII), against either a homologous or heterologous pathogen. We have shown that systemic Bacillus Calmette- Guerin (BCG) vaccination-induced TII enhances host defence against pulmonary pneumococcal infection via increased neutrophil responses in the lung, independent of centrally trained circulating monocytes. In addition, we demonstrate that acute exposure to a microbial component, lipopolysaccharide (LPS), induces long lasting changes in airway macrophages, which leads to TII capable of protecting against pneumococcal infection but extends minimal protection against SARS-CoV-2. Lastly, we demonstrate respiratory mucosal vaccination with an unrelated Ad-vectored TB vaccine provides robust protection against SARS-CoV-2 via enhanced disease tolerance. Collectively, these studies provide valuable insight into the mechanisms of innate immune memory and associated TII and its potential as a vaccination strategy for protecting against a wide range of respiratory pathogens. | en_US |
| dc.description.degree | Doctor of Philosophy (Medical Science) | en_US |
| dc.description.degreetype | Dissertation | en_US |
| dc.description.layabstract | Over the years, human vaccines which provide protection against the intended target pathogen have also offered nonspecific protective effects against unrelated pathogens. Mounting evidence suggests that systemic or local exposure to immune stimuli such as a vaccine or microbial components from the external environment can alter innate immune cells that reside in the lung. Such alterations are known as innate immune memory and can lead to enhanced protection against a broad range of bacterial and viral infections that affect the lung. However, the mechanisms mediating such nonspecific protection are only beginning to emerge and still require further investigation. Thus, the purpose of this dissertation is to uncover the distinct mechanisms by which innate immune memory in the lung protects against different respiratory bacterial and viral infections. This will provide novel insight into the design and development of new vaccine and immunotherapeutic strategies to combat infectious diseases. | en_US |
| dc.identifier.uri | http://hdl.handle.net/11375/32338 | |
| dc.language.iso | en | en_US |
| dc.title | Harnessing Innate Immune Memory and Trained Innate Immunity Against Bacterial and Viral Infections | en_US |
| dc.type | Thesis | en_US |