Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway.
Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway.
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DOI：
10.1371/journal.ppat.1003993
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发表时间：
2014-03
期刊：
影响因子：
6.7
通讯作者：
Hel Z
中科院分区：
文献类型：
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作者：
Bowers NL;Helton ES;Huijbregts RP;Goepfert PA;Heath SL;Hel Z
HIV-1感染与T细胞功能能力的进行性丧失和对抗原刺激的反应性降低有关。HIV-1/AIDS中T细胞功能障碍的潜在机制尚未完全了解。多项研究表明，单核细胞和树突状细胞表面上的程序性死亡配体1（PD-L1）与T细胞上的PD-1的结合负调节T细胞功能。在这里，我们发现HIV-1感染者血液中的中性粒细胞表达高水平的PD-L1。PD-L1由HIV-1病毒粒子、TLR-7/8配体、细菌脂多糖（LPS）和IFNα诱导。中性粒细胞PD-L1水平与CD 4+和CD 8 + T细胞上PD-1和CD 57的表达、血浆中中性粒细胞脱粒标志物水平升高以及表达粒细胞骨髓源性抑制细胞（G-MDSC）表型的低密度中性粒细胞（LDN）频率增加相关。从HIV-1感染患者血液中纯化的中性粒细胞通过多种机制抑制T细胞功能，包括PD-L1/PD-1相互作用和活性氧簇（ROS）的产生。总的来说，累积的数据表明，慢性HIV-1感染导致中性粒细胞免疫抑制活性的诱导，其特征在于PD-L1的高表达和对T细胞功能的抑制作用。尽管进行了30年的深入研究，但我们对HIV-1病毒如何破坏免疫系统对抗常见感染的能力的了解仍然有限。虽然我们知道T细胞，一个通常对抗入侵病原体的关键细胞群，在HIV-1感染者中失去了功能，但我们并不完全理解为什么。在这里，我们发现HIV-1病毒激活另一种类型的细胞，即中性粒细胞，这是血液中最常见的白色细胞类型。活化的中性粒细胞会对T细胞的功能产生负面影响，并阻止它们产生细胞因子，细胞因子是一种保护性蛋白质，可作为信使协调对细菌和病毒的免疫反应。这种新发现的中性粒细胞介导的免疫抑制机制可能会改变我们对HIV-1发病机制的理解，并导致设计针对HIV-1/AIDS免疫功能丧失的新疗法。
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. Despite 30 years of intensive research, our understanding of how HIV-1 virus undermines the ability of the immune system to fight common infections is limited. Although we know that T cells, a key cell population that normally fights invading pathogens, lose their ability to function in HIV-1-infected individuals, we do not fully understand why. Here, we found that HIV-1 virus activates another type of cells, neutrophils, the most common type of white cell in the blood. Activated neutrophils negatively affect the function of T cells and prevent them from producing cytokines, protective proteins that serve as messengers orchestrating the immune response to bacteria and viruses. This newly identified mechanism of immune suppression mediated by neutrophils may alter our understanding of HIV-1 pathogenesis and result in a design of novel therapies targeting the loss of immune function in HIV-1/AIDS.
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感染期间淋巴结中中性粒细胞迁移的动态。
影响因子：
32.4
作者：
Chtanova, Tatyana;Schaeffer, Marie;Han, Seong-Ji;van Dooren, Giel G.;Nollmann, Marcelo;Herzmark, Paul;Chan, Shiao Wei;Satija, Harshita;Camfield, Kristin;Aaron, Holly;Striepen, Boris;Robey, Ellen A.
通讯作者：
Robey, Ellen A.
DOI：
10.1073/pnas.0600363103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Herbeuval, JP;Nilsson, J;Shearer, GM
通讯作者：
Shearer, GM
影响因子：
5.5
作者：
Buckley, Christopher D.;Ross, Ewan A.;Rainger, G. Ed
通讯作者：
Rainger, G. Ed
DOI：
10.1086/653736
发表时间：
2010-08-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Cloke TE;Garvey L;Choi BS;Abebe T;Hailu A;Hancock M;Kadolsky U;Bangham CR;Munder M;Müller I;Taylor GP;Kropf P
通讯作者：
Kropf P
影响因子：
82.9
作者：
通讯作者：
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