Vitamin E boosts resistance to Streptococcus pneumoniae infection in aged mice by inhibiting hepoxilin A3‐mediated neutrophil recruitment across the lung epithelium (392.4)

Abstract

Streptococcus pneumoniae (Sp) infections in the elderly are a significant health and economic burden. We showed that vitamin E (VE) supplementation reverses the age‐associated decline in resistance to Sp in mice. To identify mechanisms of VE‐mediated protection, young and old (2 and 22 mo, respectively) mice were fed a control (30 PPM VE) or supplemented (500 PPM VE) diet for 1 mo and then intratracheally challenged with Sp. Aged mice fed the control diet suffered excessive pulmonary inflammation relative to young mice, with almost two‐fold higher levels of neutrophil infiltration (PMNs; p= 0.0157), a feature associated with pulmonary damage and poor disease outcome. VE supplementation reduced pulmonary inflammation in old mice to levels found in young mice. VE also inhibited Sp‐induced PMN egress across polarized lung epithelial monolayers. PMN trans‐epithelial migration in response to Sp infection requires 12‐lipoxygenase‐ (12‐LO‐) dependent production of the eicosanoid hepoxilin A3 (HXA3) but VE had no effect on 12‐LO levels or activity. Rather, VE decreased the responsiveness of PMNs to HXA3. These results indicate that VE dramatically reduces age‐associated susceptibility to Sp in a murine infection model and identify HXA3 responsiveness as a key target for VE‐mediated reduction of PMN migration in aged mice.Grant Funding Source: Supported by Tufts Collaborates, ASPEN ‘13 Abbott Nutrition Grant and USDA Contract #58‐1950‐0‐014