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PLoS Pathog. 2014 Mar 13;10(3):e1003993. doi: 10.1371/journal.ppat.1003993. eCollection 2014 Mar.

Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway.

Author information

1
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
2
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.
3
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.

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.

PMID:
24626392
PMCID:
PMC3953441
DOI:
10.1371/journal.ppat.1003993
[Indexed for MEDLINE]
Free PMC Article

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