EBV up-regulates PD-L1 on the surface of primary monocytes by increasing ROS and activating TLR signaling and STAT3. Issue 4 (24th July 2018)

• Record Type: Journal Article
• Authors: Gilardini Montani, Maria Saveria; Santarelli, Roberta; Falcinelli, Luca; Gonnella, Roberta; Granato, Marisa; Di Renzo, Livia; Cuomo, Laura; Vitillo, Marina; Faggioni, Alberto; Cirone, Mara
• Is Part Of: Journal of leukocyte biology. Volume 104:Issue 4(2018)
• Page Start: 821
• Page End: 832
• Publication Date: 2018-07-24
• Subjects: EBV -- monocytes -- PD-L1 -- STAT3 -- TLR -- MAPK; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.2A0118-029RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Programmed death ligand 1 (PD-L1) (also called B7-H1) is a membrane immune-modulatory protein whose overexpression on the surface of tumor cells as well as APCs impairs T-cell-mediated killing. Viruses that establish chronic infections have developed a number of strategies to escape from immune recognition including the up-regulation of PD-L1. This study shows for the first time that the human oncovirus EBV infects human primary monocytes using HLA-DR and induced a strong up-regulation of PD-L1 expression on their surface. Searching for the underlying mechanism/s leading to this immune suppressive effect, we found that EBV activated TLR signaling, increased intracellular ROS, and phosphorylated STAT3. Targeting these molecules partially reverted PD-L1 up-regulation that correlated with an altered cytokine production and a reduction of monocyte cell survival, strongly impairing the antiviral immune response. EBV induces PD-L1 expression on the surface of infected monocytes suggesting that targeting this molecule could help to prevent or treat viral-associated diseases.