Dynamic Natural Killer Cell and T Cell Responses to Influenza Infection

Influenza viruses have perplexed scientists for over a hundred years. Yearly vaccines limit their spread, but they do not prevent all infections. Therapeutic treatments for those experiencing severe infection are limited; further advances are held back by insufficient understanding of the fundamental immune mechanisms responsible for immunopathology. NK cells and T cells are essential in host responses to influenza infection. They produce immunomodulatory cytokines and mediate the cytotoxic response to infection. An imbalance in NK and T cell responses can lead to two outcomes: excessive inflammation and tissue damage or insufficient anti-viral functions and uncontrolled infection. The main cause of death in influenza patients is the former, mediated by hyperinflammatory responses termed “cytokine storm.” NK cells and T cells contribute to cytokine storm, but they are also required for viral clearance. Many studies have attempted to distinguish protective and pathogenic components of the NK cell and T cell influenza response, but it has become clear that they are dynamic and integrated processes. This review will analyze how NK cell and T cell effector functions during influenza infection affect the host response and correlate with morbidity and mortality outcomes.