Aging Promotes Neutrophil-Induced Mortality by Augmenting IL-17 Production during Viral Infection

Older people experience enhanced susceptibility to viral infections and subsequent superimposed bacterial infections. Based on both experimental and clinical studies, this susceptibility is thought to be due to declining immune responses. However, our work indicates that older people may succumb to viral infection due to exaggerated immune responses as aged mice produce higher serum levels of the inflammatory mediator IL-17 than younger mice upon herpes viral infection. These age-elevated IL-17 responses induce a lethal immune pathology during viral infection. Early during the course of infection natural killer T-cells (NKT-cells) are major contributors to the elevated IL-17 response in aged mice. These responses synergize with defective viral clearance with aging noted by impaired IFN-alpha responses by plasmacytoid DCs. Our results indicate that novel anti-inflammatory drugs may resolve imbalanced inflammation and improve outcomes in older people infected with viruses.