NK Cells Regulate CD8+ T Cell Priming and Dendritic Cell Migration during Influenza A Infection by IFN-γ and Perforin-Dependent Mechanisms

Abstract

An effective immune response against influenza A infection depends on the generation of virus-specific T cells. NK cells are one of the first-line defenses against influenza A infection. We set out to delineate the role of NK cells in T cell immunity using a murine model of influenza A infection with A/PR/8/34. We show that early T cell recruitment mainly occurs in the posterior mediastinal lymph node (pMLN). Depletion of NK cells significantly impaired both dendritic cell (DC) and T cell recruitment into the pMLN. A similar reduction of T cell recruitment was observed when migration was blocked by pertussis toxin, suggesting that migration of pulmonary NK cells and DCs regulates cell recruitment to the pMLN. T cell recruitment was dependent on IFN-γ, and transfer of IFN-γ–competent naive NK cells into IFN-γ−/− mice restored T cell recruitment, whereas IFN-γ–deficient NK cells failed to do so. In addition, NK cell depletion reduced the uptake and transport of influenza A virus by DCs, and significantly impaired the virus-specific T cell response. Both IFN-γ−/− and perforin−/− mice showed reduced viral Ag transport by DCs, suggesting that the ability of NK cells to influence virus transport depends on IFN-γ and perforin. In summary, our data suggest that NK cells play a critical role in the initiation and shaping of the T cell response after influenza A infection.

NK-cells are involved in thymic atrophy induced by influenza A virus infection

“…Moreover, NK-cells also play important roles in bridging the innate and adaptive responses to IAV. For example, it was demonstrated that NK-cells regulated CD8 + T-cell priming and dendritic cell (DC) migration during IAV infection via IFN-c-and perforin-dependent mechanisms (Ge et al, 2012;Paust et al, 2010). However, uncovering the major and complex role of NK-cells in IAV infection requires further investigation.…”

Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation

“…25 Glycolytic reserve level is dependent on NK cells' maximum glycolytic flux and glycolysis to respond to an energetic demand. However, glycolysis was lower in ME/CFS compared to healthy controls but did not reach statistical significance.…”

Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection

“…Furthermore, production of IL-22 by NK and NKT cells has an important role in the repair of epithelial damage caused by IAV (26,27). Meanwhile, NK cells play important roles in bridging the innate and adaptive immune responses to IAV (28). The major and complex roles of NK cells in IAV infection still require further in-depth investigations.…”