Age-Related Impairment of Innate and Adaptive Immune Responses Exacerbate Respiratory Viral Infection in Older Mice

Abstract

Abstract Immune function declines with age, leading to an increased vulnerability of the elderly to respiratory viral infections. The mechanisms by which aging negatively impacts the immune system leading to enhanced susceptibility to respiratory pathogens remain to be fully elucidated. In the present study, we used a mouse model of infection with herpes simplex virus type 1 (HSV-1), a virus that can enter the lungs causing pneumonia, a rare but serious health concern in the elderly. Following intranasal inoculation of young (6 weeks), adult (36 weeks), and aged mice (68 weeks) with HSV-1 (KOS strain) we: (i) compared the local and systemic immune responses to infection in young, adult, and aged mice, and (ii) correlated the level and type of immune responses to protection against HSV-1 infection and disease. Compared to young and adult mice, the aged mice displayed: (i) increased activation of epithelial cells with a decreased expression of TLR3; (ii) increased activation of dendritic cells with increased expression of MHC-I, MHC-II, and CD80/86; and (iii) decreased production of type-I interferons; (iv) a delay in the production of anti-inflammatory cytokines and chemokines in the lungs; and (v) impairment in the frequencies of functional HSV-specific CD107+IFN-g+CD8+ T cells associated with the increased incidence of viral infection and disease. The results suggest an age-related impairment of both innate and adaptive immune responses may exacerbate respiratory viral infection and disease in the elderly.