Triphasic production of IFNγ by innate and adaptive lymphocytes following influenza A virus infection

Abstract

AbstractInterferon gamma (IFNγ) is a potent antiviral cytokine that can be produced by many innate and adaptive immune cells during infection. Currently, our understanding of which cells produce IFNγand where they are located at different stages of an infection are limited. We have used reporter mice to investigatein vivoexpression of IFNγin the lung and secondary lymphoid organs during and following influenza A virus (IAV) infection. We observed a triphasic production of IFNγexpression. Unconventional T cells and innate lymphoid cells, particularly NK cells, were the dominant producers of early IFNγ, while CD4 and CD8 T cells were the main producers by day 10 post-infection. Following viral clearance, some memory CD4 and CD8 T cells continued to produce IFNγin the lungs and draining lymph node. Interestingly, IFNγproduction by lymph node Natural Killer (NK), NKT and innate lymphoid 1 cells also continued to be above naïve levels, suggesting memory-like phenotypes for these cells. Analysis of the localisation of IFNγ+ memory CD4 and CD8 T cells demonstrated that cytokine+ T cells were located near airways and in the lung parenchyma. Following a second IAV challenge, lung IAV specific CD8 T cells rapidly increased their expression of IFNγwhile CD4 T cells in the draining lymph node increased their IFNγresponse. Together, these data suggest that IFNγproduction fluctuates based on cellular source and location, both of which could impact subsequent immune responses.