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爱泼斯坦-巴尔病毒(EBV)潜伏膜蛋白1(LMP-1)调节中间单核细胞和非经典单核细胞中的功能标志物。

Epstein Barr Virus (EBV) Latent Membrane Protein 1 (LMP-1) Regulates Functional Markers in Intermediate and Non-Classical Monocytes.

作者信息

Moyano Agustina, Colado Ana, Amarillo María Eugenia, De Matteo Elena, Preciado María Victoria, Borge Mercedes, Chabay Paola

机构信息

Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires C1425EFD, Argentina.

Laboratory of Oncological Immunology, Institute of Experimental Medicine (IMEX), CONICET-National Academy of Medicine (ANM), Buenos Aires C1425ASU, Argentina.

出版信息

Cancers (Basel). 2024 Dec 14;16(24):4169. doi: 10.3390/cancers16244169.

Abstract

: The Epstein-Barr virus (EBV) infects more than 90 percent of the human population. In pediatric patients, the innate immune response against EBV primary infection plays a key role. Monocytes and macrophages can have distinct functions depending on the microenvironment surrounding them. At least three monocyte subpopulations can be differentiated depending on membrane protein expression: classical (C, CD14++CD16-), intermediate (I, CD14++CD16+), and non-classical (NC, CD14+CD16++). They also modulate T and B lymphocyte activation/inhibition through the expression of costimulatory molecules such as CD80, CD86, and PD-L1. Yet, little is known about monocytes' role in EBV infection. : Peripheral blood and tonsil biopsies of EBV primary infected (PI) patients, healthy carriers (HCs), and patients undergoing reactivation (R) were studied. : Classical monocytes prevailed in all infectious statuses. Tonsillar CD163 positively correlated with CD163 expression in NC monocytes in HCs. PD-L1+ cells in the tonsil positively correlated with PD-L1 expression in NC monocytes. LMP-1 viral latent protein presented a positive correlation with PD-L1, CD163, and CD206 expression in the NC subpopulation. : Our results evidence the predominant role of I and NC monocytes' response against EBV infection. Furthermore, the viral oncoprotein LMP-1 could be involved in the expression of regulatory proteins in I and NC monocytes.

摘要

爱泼斯坦-巴尔病毒(EBV)感染了超过90%的人类。在儿科患者中,针对EBV原发性感染的先天免疫反应起着关键作用。单核细胞和巨噬细胞的功能可能因其周围的微环境而异。根据膜蛋白表达,至少可以区分出三个单核细胞亚群:经典型(C,CD14++CD16-)、中间型(I,CD14++CD16+)和非经典型(NC,CD14+CD16++)。它们还通过共刺激分子如CD80、CD86和PD-L1的表达来调节T和B淋巴细胞的激活/抑制。然而,关于单核细胞在EBV感染中的作用知之甚少。

对EBV原发性感染(PI)患者、健康携带者(HCs)和正在经历病毒再激活(R)的患者的外周血和扁桃体活检进行了研究。

经典单核细胞在所有感染状态中占主导。扁桃体中的CD163与HCs中NC单核细胞的CD163表达呈正相关。扁桃体中的PD-L1+细胞与NC单核细胞中的PD-L1表达呈正相关。潜伏膜蛋白1(LMP-1)病毒潜伏蛋白在NC亚群中与PD-L1、CD163和CD206表达呈正相关。

我们的结果证明了I型和NC型单核细胞对EBV感染反应的主要作用。此外,病毒癌蛋白LMP-1可能参与I型和NC型单核细胞中调节蛋白的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be02/11674279/5a74609e52e7/cancers-16-04169-g001.jpg

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