S106 Influenza Infection of Human Lung Macrophages Increases PDL1 Expression
Background & Objective Influenza infection has recently been shown to cause rapid functional impairment of CD8+ T cell responses in a murine infection model via the PD1/PDL1 pathway.1 In this mouse model, it was the induction of PDL1 that was required for this impairment of CD8+ function. A previous study suggested that the anti-inflammatory cytokine, IL-10, was the principal driver of human macrophage PDL1 expression in response to HIV infection.2 The aim of this study was to investigate how human lung macrophages regulate their PDL1 expression in response to influenza infection.
Methods Alveolar macrophages washed from resected human lung tissue and purified by plate adherence or human positively-isolated CD14+ monocyte-derived macrophages (MDMs) were cultured with H3N2 X31 influenza virus or a UV-irradiated aliquot of virus (UVX31) for 2 h, after which the cultures were washed and media replaced and incubation continued for a further 22 h. Virally infected cells and expression of cell surface markers were identified using flow cytometry. Gene expression was measured using RT-PCR.
Results No increase in MDM infection was seen using the UVX31 but incubation with X31 resulted in an average infection rate of 9.1%. Infection with X31 significantly increased cell surface expression of HLA-DR and PDL1 (p<0.05), but not of PDL2 by MDMs as measured by flow cytometry. Using RT-PCR, we observed an increase of PDL1 mRNA after X31 infection suggesting that the expression of 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. In contrast we observed a trend towards decreased expression of IL-10 mRNA. In further experiments, infection of alveolar macrophages with X31 also caused significant increases in HLA-DR and PDL1 cell surface expression.
Conclusions These data indicate that, in contrast to HIV infection of macrophages2 influenza-induced expression of PDL1 may not be regulated by IL-10 in human macrophages.
Erickson et al (2012) J Clin Invest doi: 10.1172/JCI62860.
Rodriguez-Garcia, et al. (2011) J Leukoc Biol 89(4):507–15.