Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway.
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-03-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3953441?pdf=render |
| _version_ | 1829117130089431040 |
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| author | Nathan L Bowers E Scott Helton Richard P H Huijbregts Paul A Goepfert Sonya L Heath Zdenek Hel |
| author_facet | Nathan L Bowers E Scott Helton Richard P H Huijbregts Paul A Goepfert Sonya L Heath Zdenek Hel |
| author_sort | Nathan L Bowers |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T20:21:34Z |
| format | Article |
| id | doaj.art-83303f7c6dcb42d383f87d587b4720f7 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-12T20:21:34Z |
| publishDate | 2014-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-83303f7c6dcb42d383f87d587b4720f72022-12-22T00:13:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-03-01103e100399310.1371/journal.ppat.1003993Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway.Nathan L BowersE Scott HeltonRichard P H HuijbregtsPaul A GoepfertSonya L HeathZdenek HelHIV-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.http://europepmc.org/articles/PMC3953441?pdf=render |
| spellingShingle | Nathan L Bowers E Scott Helton Richard P H Huijbregts Paul A Goepfert Sonya L Heath Zdenek Hel Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. PLoS Pathogens |
| title | Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. |
| title_full | Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. |
| title_fullStr | Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. |
| title_full_unstemmed | Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. |
| title_short | Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. |
| title_sort | immune suppression by neutrophils in hiv 1 infection role of pd l1 pd 1 pathway |
| url | http://europepmc.org/articles/PMC3953441?pdf=render |
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