title: The α-tocopherol form of vitamin E reverses age-associated susceptibility to streptococcus pneumoniae lung infection by modulating pulmonary neutrophil recruitment.
abstract: Streptococcus pneumoniae infections are an important cause of morbidity and mortality in older patients. Uncontrolled neutrophil-driven pulmonary inflammation exacerbates this disease. To test whether the α-tocopherol (α-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. pneumoniae, young (4 mo) and old (22-24 mo) C57BL/6 mice were fed a diet containing 30-PPM (control) or 500-PPM (supplemented) α-Toc for 4 wk and intratracheally infected with S. pneumoniae. Aged mice fed a control diet were exquisitely more susceptible to S. pneumoniae 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, α-Toc supplementation of aged mice resulted in a 1000-fold lower bacterial lung burden and full control of infection. This α-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. α-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. α-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 α-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.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111;
authors.forename: Elsa N
authors.initials: EN
authors.lastname: Bou Ghanem
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111;
authors.forename: Stacie
authors.initials: S
authors.lastname: Clark
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston MA 02114; and.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Du
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston MA 02114; and.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111; Howard Hughes Medical Institute, Boston, MA 02111.
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111; simin.meydani@tufts.edu john.leong@tufts.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Leong
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston MA 02114; and simin.meydani@tufts.edu john.leong@tufts.edu.
authors.forename: Simin N
authors.initials: SN
authors.lastname: Meydani
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000187:drug effects / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology*; D004848:Epithelium / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000276:immunology; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; C038243:8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D024502:alpha-Tocopherol