Abstract
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.
Highlights
Influenza is a rapidly mutating RNA virus which causes yearly global epidemics characterized by about 1 billion infections and 290,000–650,000 deaths (Iuliano et al, 2018)
CXCL16 expression in the lung is important in CXCR6+ T cell homing; this is responsible for the recruitment and maintenance of TRM cells in the airways following influenza infection in mice (Morgan et al, 2005; Wein et al, 2019)
Type I IFNs, IL-27, and IL-2 contribute to stimulating NK cell and CD4 T cell antiviral function; induction of CD8+ T cell IL-10 production by these signaling molecules is significant and should be considered in studies which use the presence of these cytokines as a measure of immune activation or host resistance to influenza infection
Summary
Reviewed by: Stephanie Jost, Beth Israel Deaconess Medical Center and Harvard Medical School, United States Namal P. Influenza viruses have perplexed scientists for over a hundred years 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. 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
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