Age-dependent susceptibility to a viral disease due to decreased natural killer cell numbers and trafficking.

Although it is well known that aged hosts are generally more susceptible to viral diseases than the young, specific dysfunctions of the immune system directly responsible for this increased susceptibility have yet to be identified. We show that mice genetically resistant to mousepox (the mouse parallel of human smallpox) lose resistance at mid-age. Surprisingly, this loss of resistance is not a result of intrinsically defective T cell responses. Instead, the primary reason for the loss of resistance results from a decreased number of total and mature natural killer (NK) cells in the blood and an intrinsic impairment in their ability to migrate to the lymph node draining the site of infection, which is essential to curb systemic virus spread. Hence, our work links the age-dependent increase in susceptibility to a viral disease to a specific defect of NK cells, opening the possibility of exploring treatments to improve NK cell function in the aged with the goal of enhancing their resistance to viral diseases.