Yao Wen-Rong, Li Dong, Yu Lei, Wang Feng-Jie, Xing Hui, Yang Gui-Bo
National Center for AIDS/STD Control and Prevention, China CDC, 155 Changbai Road, Changping District, Beijing, 102206, People's Republic of China.
Immunol Res. 2017 Aug;65(4):869-879. doi: 10.1007/s12026-017-8925-z.
Dendritic cell NK lectin Group Receptor-1 (DNGR-1), also known as C-type lectin domain family 9, member A (CLEC9A), is a member of C-type lectin receptor superfamily expressed primarily on dendritic cells (DC) that excel in cross-presentation of exogenous antigens. To find out whether and how it is affected in human immunodeficiency virus infections or acquired immunodeficiency syndromes (HIV/AIDS), DNGR-1 expression and DNGR-1-binding cells in simian/human immunodeficiency virus (SHIV) and simian immunodeficiency virus (SIV)-infected rhesus macaques and antiretroviral therapy (ART)-treated AIDS patients were examined by real-time RT-PCR, flow cytometry, and confocal microscopy. DNGR-1 expression was observed in both lymphoid and non-lymphoid tissues including gut-associated lymphoid tissues (GALT) of rhesus macaques. DNGR-1 mRNA levels were significantly reduced in the blood while significantly elevated in the GALT of SHIV/SIV-infected rhesus macaques. DNGR-1 transcription levels were also significantly reduced in the blood of ART-treated AIDS patients irrespective of viral status. White blood cells with exposed DNGR-1 ligands were significantly increased in ART-treated AIDS patients, while significantly decreased in SIV-infected rhesus macaques. These data indicate that DNGR-1 expression, and by extension, the function of cross-presentation of antigens associated with dead/damaged cells might be compromised in HIV/SIV infection, which might play a role in HIV/AIDS pathogenesis and should be taken into consideration in therapeutic AIDS vaccine development.
树突状细胞NK凝集素组受体-1（DNGR-1），也称为C型凝集素结构域家族9成员A（CLEC9A），是C型凝集素受体超家族的成员，主要表达于在交叉呈递外源性抗原方面表现出色的树突状细胞（DC）上。为了弄清楚它在人类免疫缺陷病毒感染或获得性免疫缺陷综合征（HIV/AIDS）中是否以及如何受到影响，通过实时逆转录聚合酶链反应、流式细胞术和共聚焦显微镜检查了感染猿猴/人类免疫缺陷病毒（SHIV）和猿猴免疫缺陷病毒（SIV）的恒河猴以及接受抗逆转录病毒疗法（ART）治疗的艾滋病患者的DNGR-1表达和DNGR-1结合细胞。在恒河猴的包括肠道相关淋巴组织（GALT）在内的淋巴组织和非淋巴组织中均观察到DNGR-1表达。在SHIV/SIV感染的恒河猴的血液中，DNGR-1 mRNA水平显著降低，而在GALT中显著升高。无论病毒状态如何，接受ART治疗的艾滋病患者血液中的DNGR-1转录水平也显著降低。在接受ART治疗的艾滋病患者中，暴露有DNGR-1配体的白细胞显著增加，而在感染SIV的恒河猴中显著减少。这些数据表明，在HIV/SIV感染中，DNGR-1的表达以及与之相关的死亡/受损细胞抗原交叉呈递功能可能受到损害，这可能在HIV/AIDS发病机制中起作用，并且在治疗性艾滋病疫苗开发中应予以考虑。
