LSC 2014 abstract - Influenza infection of human lung macrophages increases PDL1 expression via autologous IFN{beta}

Lung macrophages are an important defence against influenza infection, but macrophage function can be dysregulated by infection. Recent work has shown that acute immune responses to influenza in the murine lung are regulated by PDL1 expression leading to rapid modulation of CD8+ T cell responses via the PD1 receptor1. This PD1/PDL1 pathway may modulate acute inflammatory responses to prevent tissue damage. The aim of the present study was to investigate how human macrophages regulate their PDL1 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. Infection significantly increased cell surface expression of PDL1 on lung macrophages and MDM. Using RT-PCR, we observed an increase of PDL1 mRNA after X31 as well as an increase in type I interferon expression by MDMs in response to X31 infection. Using siRNA targeting IFNα and IFNβ, we observed a ~45% reduction in the mRNA expression of both of these cytokines in response to infection, but only IFNβ siRNA reduced the influenza-induced expression of PDL1 mRNA by ~30%. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that influenza-induced release of IFNβ by macr...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: 10.1 Respiratory Infections Source Type: research