|BOU GHANEM, ELSA - Tufts University|
|CLARK, STACIE - Tufts University|
|DU, XIAOGANG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|CAMILLI, ANDREW - Tufts University|
|LEONG, JOHN - Tufts University|
|MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/10/2014
Publication Date: 1/15/2015
Citation: Bou Ghanem, E.N., Clark, S., Du, X., Wu, D., Camilli, A., Leong, J.M., Meydani, S.N. 2015. The alpha-tocopherol form of vitamin E reverses age-associated susceptibility to Streptococcus pneumoniae lung infection by modulating pulmonary neutrophil recruitment. Journal of Immunology. 194:1090-1099. https://doi.org/10.4049/jimmunol.1402401.
Interpretive Summary: During aging, the body's immune function declines and becomes dysregulated. As such, aging increases the risk for developing lung infections like Streptococcus pneumoniae, one of the most common types of pneumonia in the elderly. The aim of this study was to test whether vitamin E supplemented in the diet can protect aged mice from getting disease caused by Streptococcus pneumoniae. We found that feeding extra vitamin E to aged mice reversed their vulnerability to disease caused by this bacterium. Vitamin E regulated the aged mice's immune responses, which allowed them to fight lung infection more efficiently. As the first step to translate these results to humans, we conducted studies using human cells and found that vitamin E also improved the response of human cells. These findings show promise for the future use of vitamin E to fight lung infection in the elderly.
Technical Abstract: Streptococcus pneumonia infections are an important cause of morbidity and mortality in older patients. Uncontrolled neutrophil-driven pulmonary inflammation exacerbates this disease. To test whether the alpha-tocopherol (alpha-Toc) form of vitamin E, a regulator of immunity, can modulate neutrophil responses as a preventive strategy to mitigate the age-associated decline in resistance to S. pneumonia, young (4 mo) and old (22-24 mo) C57BL/6 mice were fed a diet containing 30-PPM (control) or 500-PPM (supplemented) alpha-Toc for 4 wk and intratracheally infected with S. pneumoniae. Aged mice fed a control diet were exquisitely more susceptible to S. pneumonia than young mice. At 2 d postinfection, aged mice suffered 1000-fold higher pulmonary bacterial burden, 2.2-fold higher levels of neutrophil recruitment to the lung, and a 2.25-fold higher rate of lethal septicemia. Strikingly, alpha-Toc supplementation of aged mice resulted in a 1000-fold lower bacterial lung burden and full control of infection. This alpha-Toc-induced resistance to pneumococcal challenge was associated with a 2-fold fewer pulmonary neutrophils, a level comparable to S. pneumoniae-challenged, conventionally fed young mice. alpha-Toc directly inhibited neutrophil egress across epithelial cell monolayers in vitro in response to pneumococci or hepoxilin-A3, an eicosanoid required for pneumococcus-elicited neutrophil trans-epithelial migration. alpha-Toc altered expression of multiple epithelial and neutrophil adhesion molecules involved in migration, including CD55, CD47, CD18/CD11b, and ICAM-1. These findings suggest that alpha-Toc enhances resistance of aged mice to bacterial pneumonia by modulating the innate immune response, a finding that has potential clinical significance in combating infection in aged individuals through nutritional intervention.