In conclusion, we demonstrate that efficient NK cell activity contributes to the optimal orchestration of innate and adaptive immunity during the course of a viral infection in vivo. The implications of these findings extend to the design of therapeutic strategies to fight human disease in two ways, as they emphasize i) that the benefits of innate cytokine production for immune cell recruitment and activation can be outweighed by detrimental effects that can directly reduce the capacity of the host to fight infection, as well as ii) the need to better understand and take into account the complex interactions of relatively rare cell types that occur in a physiological context for the purpose of exploiting the human immune system to promote health over disease.