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Dissertation
Nutritional modulation of the innate immune response to influenza infection
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2007
DOI:
https://doi.org/10.17918/etd-1787
Abstract
Natural killer (NK) cells play an important role in controlling virus infections and provide a potential target for nutritional modulations that may alter the innate immune response to viruses. Data presented here provide direct evidence that 1) NK cells limit influenza virus in the lung early following infection, 2) an age-associated defect in inducible NK cell cytotoxicity contributes to the increased susceptibility of aged mice to primary influenza infection, and 3) NK cells respond, both positively and negatively, to nutritional interventions. Caloric restriction (CR) is a nutritional intervention that has been shown to extend lifespan in mice and postpone age-related changes in immunity. However, in our studies, aged (22 mo) CR mice exhibited increased mortality, impaired viral clearance, and reduced natural killer (NK) cell activity following influenza infection compared to aged ad-libitum (AL) mice. To determine if these detrimental effects of CR occur independently of advanced age, young adult (6 mo) CR and AL C57BL/6 mice were infected with 104 TCID50/100 HAU of influenza A virus (H1N1, PR8). The CR mice exhibited increased mortality (P<0.05), weight loss (P<0.01), lung virus titers (P<0.05), and lung pathology (P<0.001) compared to young AL controls. Also, CR mice exhibited a decrease in total (P<0.001) and NK1.1+ lymphocytes (P<0.05) compared to AL in response to infection, as well as a reduction in influenza-induced NK cell cytotoxicity in both lung (P<0.01) and spleen (P<0.05). These data are the first to describe an age-independent and detrimental effect of CR on the innate immune response to influenza infection. In a separate study, young (6-8wk) C57BL/6 mice were supplemented with 1g/kg body weight of active hexose correlated compound (AHCC), a fermented mushroom extract, for 7 days prior to and throughout infection with 100 HAU of influenza A virus (H1N1, PR8). Supplementation increased survival and decreased weight loss (P<0.001) in response to influenza infection. Further, supplementation increased NK cell activity in lung at 1 day p.i. (P<0.05) and 4 days p.i. (P<0.01) and in spleen at 2 days p.i. (P<0.01). In conclusion, NK cells are important in controlling primary influenza infection, and both aging and nutritional status alter this response.
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Details
- Title
- Nutritional modulation of the innate immune response to influenza infection
- Creators
- Barry W. Ritz - DU
- Contributors
- Elizabeth M. Gardner (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Bioscience and Biotechnology [Historical]; College of Arts and Sciences; Drexel University
- Other Identifier
- 1787; 991014632698904721