title: Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway.
abstract: 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.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Bowers
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: E Scott
authors.initials: ES
authors.lastname: Helton
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Richard P H
authors.initials: RP
authors.lastname: Huijbregts
authors.affiliation: Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heath
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Hel
mesh_terms: D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor