Increased levels of soluble co-stimulatory molecule PD-L1 (B7-H1) in the plasma of viraemic HIV-1+ individuals

Abstract

Recent evidence has revealed that PD-L1 is expressed in two functional forms, namely, a membrane-bound form (mPD-L1) and a soluble form (sPD-L1). The identification of the soluble form of PD-L1 represents the discovery of a new potential mechanism for the activation of the PD-1 pathway that may mediate a physiological apoptotic mechanism through a cell-cell signalling-independent pathway and may also favour T cell dysfunction during HIV infection. Since the presence of sPD-L1 has not been well established in the scenario of chronic viral infection, we investigated the presence of sPD-L1 in the plasma of viraemic HIV+ individuals and the potential mechanism that promotes its production. We report the following: 1) the level of the soluble form of PD-L1 is increased in the plasma of viraemic HIV+ individuals, 2) the level of the soluble form of PD-L1 in viraemic HIV+ individuals correlates with markers of microbial product translocation and inflammation, 3) the expression of the membrane-bound form of PD-L1 on conventional dendritic cells from viraemic HIV+ individuals correlates with the levels of soluble PD-L1 and MMP-2, and 4) monocyte-derived dendritic cells not only increase their expression of mPD-L1 and MMP-2 but also produce sPD-L1 after LPS and TNF-α stimulation, as demonstrated by functional in vitro experiments, which provides insight into the potential source of sPD-L1 production.