|BOU GHANEM, ELSA - Friedman School At Tufts|
|LEE, JAMES - Tufts University|
|JOMA, BASMA - Tufts University|
|MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|LEONG, JOHN - Tufts University|
|PANDA, ALEXANDER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Frontiers in Cellular and Infection Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/12/2017
Publication Date: 5/3/2017
Citation: Bou Ghanem, E.N., Lee, J.N., Joma, B.H., Meydani, S.N., Leong, J.M., Panda, A. 2017. The alpha-tocopherol form of vitamin E boosts elastase activity of human PMNs and their ability to kill Streptococcus pneumoniae. Frontiers in Cellular and Infection Microbiology. doi: 10.3389/fcimb.2017.00161.
Interpretive Summary: We previously found that vitamin E supplementation in old mice helps fight bacterial pneumonia caused by Streptococcus pneumoniae (pneumococci) by boosting the ability of innate immune cells called neutrophils to kill bacteria and by regulating their movement into the infected lungs. In this study, we wanted to test the effect of aging and vitamin E on neutrophil behavior in elderly versus young people. We found that neutrophils from old and young individuals move towards the infection in a similar manner. Surprisingly, we found neutrophils from older donors killed the pneumococcal bacteria better than young donors. Vitamin E treatment of neutrophils isolated from the blood of donors increased the ability of these cells to kill the pneumococcal bacteria by increasing the activity of an enzyme called neutrophil elastase, which helps fight infection. These findings demonstrate that vitamin E is a powerful regulator of neutrophil responses and is a potential nutritional intervention to combat pneumococcal pneumonia.
Technical Abstract: Despite the availability of vaccines, Streptococcus pneumoniae remains a leading cause of life-threatening infections such as pneumonia, bacteremia and meningitis. Polymorphonuclear leukocytes (PMNs) are a key determinant of disease course, because optimal host defense requires an initial robust pulmonary PMN response to control bacterial numbers followed by modulation of this response later in infection. The elderly, who manifest a general decline in immune function and higher basal levels of inflammation, are at increased risk of developing pneumococcal pneumonia. Using an aged mouse infection model, we previously showed that oral supplementation with the alpha-tocopherol form of vitamin E (alpha-Toc) decreases pulmonary inflammation, in part by modulating neutrophil migration across lung epithelium into alveolar spaces, and reverses the age-associated decline in resistance to pneumococcal pneumonia. The objective of this study was to test the effect of alpha-Toc on the ability of neutrophils isolated from young (22-35 years) or elderly (65-69 years) individuals to migrate across epithelial cell monolayers in response to S. pneumoniae and to kill complement-opsonized pneumococci. We found that basal levels of pneumococcal-induced transepithelial migration by PMNs from young or elderly donors were indistinguishable, suggesting that the age-associated exacerbation of pulmonary inflammation is not due to intrinsic properties of PMNs of elderly individuals but rather may reflect the inflammatory milieu of the aged lung. Consistent with its anti-inflammatory activity, alpha-Toc treatment diminished PMN migration regardless of donor age. Unexpectedly, unlike previous studies showing poor killing of antibody-opsonized bacteria, we found that PMNs of elderly donors were more efficient at killing complement-opsonized bacteria ex vivo than their younger counterparts. We also found that the heightened antimicrobial activity in PMNs from older donors correlated with increased activity of neutrophil elastase, a serine protease that is required to kill pneumococci. Notably, incubation with alpha-Toc increased PMN elastase activity from young donors and boosted their ability to kill complement-opsonized pneumococci. These findings demonstrate that alpha-Toc is a potent modulator of PMN responses and is a potential nutritional intervention to combat pneumococcal infection.