TY - JOUR T1 - Influenza infection of human lung macrophages increases PDL1 expression JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P1883 AU - Karl J. Staples AU - Ben Nicholas AU - C. Mirella Spalluto AU - Richard T. McKendry AU - Ratko Djukanovic AU - Tom M.A. Wilkinson Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P1883.abstract N2 - Macrophages are an important defence against influenza infection in the human lung. However infection of macrophages themselves can dysregulate cellular function contributing to secondary bacterial infections that are postulated to be the prime causes of mortality due to influenza. Recent work has shown that acute immune responses to influenza are modulated by the T cell exhaustion pathway with increased lung PD-L1 expression leading to rapid impairment of CD8+ T cell responses in a murine model1. The aim of the present study was to investigate how human macrophages regulate their PD-L1 expression in response to influenza infection. Human lung and monocyte-derived macrophages (MDMs) were exposed to H3N2 X31 influenza virus or UV-irradiated virus (UVX31). No infection of lung macrophages or MDM was seen upon exposure to UVX31 but incubation with X31 resulted in a mean infection rate of 18% and 29% respectively. Influenza infection significantly increased cell surface expression of PD-L1 on lung macrophages and MDM as measured by flow cytometry. Using RT-PCR, we observed an increase of PD-L1 mRNA after X31 infection suggesting that this protein is transcriptionally regulated. In addition, we saw an increase in type I interferon expression by MDMs in response to X31 infection, but no expression of IFNγ. When MDM were incubated with IFNβ, this cytokine caused increased expression of PD-L1 steady state mRNA. These data indicate that influenza-induced release of type I IFNs by macrophages regulates surface expression of PD-L1, which may predispose to secondary bacterial infection by impairing CD8 T cell function.1. Erickson et al (2012) J Clin Invest doi: 10.1172/JCI62860. ER -