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Immune Suppression by Neutrophils in HIV-1 Infection: Role of PD-L1/PD-1 Pathway
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Immune Suppression by Neutrophils in HIV-1 Infection: Role of PD-L1/PD-1 Pathway
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Journal Article
Immune Suppression by Neutrophils in HIV-1 Infection: Role of PD-L1/PD-1 Pathway
2014
Overview
HIV-1 infection is associated with a progressive loss of T cell functional capacity and reduced responsiveness to antigenic stimuli. The mechanisms underlying T cell dysfunction in HIV-1/AIDS are not completely understood. Multiple studies have shown that binding of program death ligand 1 (PD-L1) on the surface of monocytes and dendritic cells to PD-1 on T cells negatively regulates T cell function. Here we show that neutrophils in the blood of HIV-1-infected individuals express high levels of PD-L1. PD-L1 is induced by HIV-1 virions, TLR-7/8 ligand, bacterial lipopolysaccharide (LPS), and IFNα. Neutrophil PD-L1 levels correlate with the expression of PD-1 and CD57 on CD4+ and CD8+ T cells, elevated levels of neutrophil degranulation markers in plasma, and increased frequency of low density neutrophils (LDNs) expressing the phenotype of granulocytic myeloid-derived suppressor cells (G-MDSCs). Neutrophils purified from the blood of HIV-1-infected patients suppress T cell function via several mechanisms including PD-L1/PD-1 interaction and production of reactive oxygen species (ROS). Collectively, the accumulated data suggest that chronic HIV-1 infection results in an induction of immunosuppressive activity of neutrophils characterized by high expression of PD-L1 and an inhibitory effect on T cell function.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Acquired immune deficiency syndrome
/ AIDS
/ Biology
/ Cancer
/ CD4-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Humans
/ Immune Tolerance - immunology
/ Ligands
/ Medicine
/ Programmed Cell Death 1 Receptor - immunology
/ Programmed Cell Death 1 Receptor - metabolism
/ Rodents
/ Software
