Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection

Abstract

Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.

Replicative fitness of transmitted HIV-1 drives acute immune activation, proviral load in memory CD4 + T cells, and disease progression

“…We found that vRC was positively correlated with a number of inflammatory cytokines (Table 2), most notably IL-6 and IL-1β, two proinflammatory cytokines previously implicated in driving aberrant CD4 + T-cell turnover and impairing homeostatic proliferation (21). Of note, vRC was also strongly correlated with elevated levels of IL-10, an important antiinflammatory cytokine linked to T-cell dysfunction in HIV infection (22,23).…”

Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

“…5 It was reported that the level of monocyte turnover was more pronounced than the viral load and lymphocyte activation in SIVinfected rhesus macaques; this finding implied that monocytes may be very important in the pathogenesis of AIDS. As a result of high TLR4 and CD14 expression, monocytes in the plasma of HIV patients were sensitive to high levels of LPS and inflammatory cytokines; 17 this result implied that the role of LPS is important in the pathogenesis of AIDS.…”

Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

“…LPS, also known as lipoglycan, is found in the outer membrane of Gramnegative bacteria, and acts as an endotoxin and elicits strong immune responses in animals. LPS acts as a prototypical endotoxin due to its binding to the CD14/ TLR4/MD2 receptor complex, which promotes the secretion of pro-inflammatory cytokines in a variety of cell types (Reid et al, 1997;Boes et al, 1998;Said et al, 2010).…”