Obesity is a serious health issue in the United States as well as worldwide and contributes to several other disorders such as cardiovascular diseases, type II diabetes and asthma. However, the impact of obesity on immune responses to infections is poorly understood. During the last decade, specifically after the 2009 H1N1 strain influenza pandemic, evidence has emerged that obesity increases the risk and worsens the outcome for infection by influenza A virus (IAV). Obese individuals were hospitalized at a higher rate compared to their lean counterparts, had longer hospitalization times, responded poorly to vaccination and had increased mortality. Host protection and clearance of respiratory pathogens like IAV require robust pulmonary immune responses. Since alveolar macrophages (AM) are the first line of defense against respiratory pathogens, we hypothesized that obesity-associated alterations in AM functions worsen IAV infection outcomes. To test this hypothesis I fed C57BL/6 mice with a low-fat or high-fat diet for different time periods and infected these animals with an H1N1 laboratory strain of IAV (PR/8). Mice on the high-fat diet (obese mice) showed increased morbidity and mortality upon infection as compared with mice on the low-fat diet (lean mice). I also found that obesity induces changes in overall lung cellularity, AM polarization and phagocytic ability, and alterations in the level of surface proteins such as Gal-3, MHC-II, Tim-3, and cytokines such as IL-6, TNF-?, IFN-? and IL-10 in the lung. These obesity-induced changes in AM may contribute to impaired immune responses during IAV infection, resulting in worsened outcomes.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04182016-171359 |
| Date | 19 April 2016 |
| Creators | Kumar, Aaram Abhiram |
| Contributors | Luc Van Kaer, Stokes Peebles |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-04182016-171359/ |
| Rights | restrictone, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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