Age-Related Impairment of Innate and Adaptive Immune Responses Following Intranasal Herpes Simplex Infection

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