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 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. © 2014 bowers et al.