Immune Suppression by Neutrophils in HIV-1 Infection: Role of PD-L1/PD-1 Pathway

PLoS Pathogens

Paul A. Goepfert¹  Zdenek Hel¹  Sonya L. Heath²  Richard P. H. Huijbregts³  Nathan L. Bowers³  E. Scott Helton³ 

[1] 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;Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America

关键词: Neutrophils;    T cells;    HIV-1;    Blood;    Monocytes;    Blood plasma;    Cytotoxic T cells;    Enzyme-linked immunoassays;   

DOI  :  10.1371/journal.ppat.1003993

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY