AUTHOR=Liu Kai , Huang Hui-Huang , Yang Tao , Jiao Yan-Mei , Zhang Chao , Song Jin-Wen , Zhang Ji-Yuan , Zhou Chun-Bao , Yuan Jin-Hong , Cao Wen-Jing , Mu Xiu-Ying , Zhou Ming-Ju , Li Hua-Jie , Shi Ming , Xu Ruonan , Wang Fu-Sheng 

TITLE=Increased Neutrophil Aging Contributes to T Cell Immune Suppression by PD-L1 and Arginase-1 in HIV-1 Treatment Naïve Patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.670616

DOI=10.3389/fimmu.2021.670616

ISSN=1664-3224

ABSTRACT=Neutrophils are characterized by heterogeneity, with capacity to fight against pathogens, and involved in tissue injury repair and immune system regulation. Generally, neutrophils have a very short life span in the peripheral blood, and undergone the process of aging after release from bone marrow. Under some pathological conditions, the over-aggregation of aged neutrophils occurred and is associated with phenotypic and functional change, which may lead to T cell immuno-dysfunction. During HIV-1 infection, the dynamics of neutrophil aging and its role in mediating T cell exhaustion are not well understood. In the study, we enrolled 23 treatment naïve (TN) patients, 23 ART (antiretroviral therapy)-treated individuals and 21 healthy controls (HC). In these cohorts we measured the status of aged neutrophils and the correlation with T cell activation levels. In TN patients, peripheral neutrophils have a significantly higher aging phenotype and were over-activated. The aging of neutrophils is positively correlated with HIV-1 RNA levels, and have impaired reactive oxygen species (ROS) production after LPS stimulation. Simultaneously, aged neutrophils were characterized by increased PD-L1 and arginase-1 expression in a time-depended manner. The aged neutrophils demonstrated a higher capacity to inhibit CD8+ T cell secreting IFN-γ and TNF-α compared to non-aged neutrophils. The inhibition effect was reversed by anti-PD-L1 and anti-arginase-1 blocking in vitro. Finally, LPS was identified as an important activator to initiate the process of neutrophil aging. These results provide evidence that dampening neutrophil aging may provide a novel approach to recover T cell dysfunction in HIV-1 patients.