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The Lung Mucosa and Its Impact on Mycobacterium tuberculosis Pathogenesis and Bacillus Calmette-Guerin Vaccine Efficacy
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | The Lung Mucosa and Its Impact on Mycobacterium tuberculosis Pathogenesis and Bacillus Calmette-Guerin Vaccine Efficacy. |
| 개인저자 | Moliva, Juan Ignacio. |
| 단체저자명 | The Ohio State University. Biomedical Sciences. |
| 발행사항 | [S.l.]: The Ohio State University., 2017. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2017. |
| 형태사항 | 314 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781687948540 |
| 학위논문주기 | Thesis (Ph.D.)--The Ohio State University, 2017. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Torrelles, Jordi. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is the current leading cause of death due to a single infectious organism. Although curable, the broad emergence of drug resistant M.tb strains has hindered eradication efforts. Furthermore, computational models predict a quarter of the world's population is infected with M.tb in a latent state, effectively serving as the largest reservoir of any human pathogen with the ability to cause significant global morbidity and mortality. Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the only vaccine approved for use to prevent TB. In humans, BCG is highly efficacious against disseminated forms of TB, but fails to fully protect against the development of pulmonary TB. Thus, new vaccination strategies are urgently needed if we are to eradicate this pathogen. The World Health Organization has prioritized research and development of novel TB vaccines, however our incomplete understanding on the requirements for protective immunity to M.tb has made it difficult to develop new successful vaccines. In this collective work, we explore how manipulation of the mycobacterial cell wall can further advance our knowledge of M.tb pathogenesis and the development of effective protective immunity.The microenvironment of the lung has emerged as an important contributor to antimicrobial immunity, especially in the context of M.tb. Homeostatic components within the alveolar lining fluid (ALF) of the lung mucosa have been shown to play a significant role in the pathogenesis of M.tb via modulation of host immunity. Previous studies demonstrated that exposure of M.tb to human ALF can modify the M.tb cell wall, stripping virulent lipids, glycolipids, and lipoglycans used by M.tb to subvert host immunity. This interaction renders M.tb more susceptible to killing by host immune cells. We demonstrate that human ALF can affect the development of mycobacterial-specific immunity by BCG in the lung, increasing its efficacy against M.tb pathogenesis and virulence. These results led us to hypothesize that effective pulmonary immunity against M.tb brought forth by BCG can be improved by taking into consideration the influence of cell wall lipids, glycolipids, and lipoglycans on the development of immunological responses. We uncovered that chemical treatment of BCG with the aliphatic hydrocarbon solvent petroleum ether accomplishes similar effects as human ALF |
| 일반주제명 | Biochemistry. Immunology. Microbiology. Cellular biology. Biomedical engineering. |
| 언어 | 영어 |
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