INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Infrastructure, CEA-Université Paris Sud 11, Fontenay-aux-Roses, France.
INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
Front Immunol. 2020 Sep 8;11:2096. doi: 10.3389/fimmu.2020.02096. eCollection 2020.
Viral vectors are increasingly used as delivery means to induce a specific immunity in humans and animals. However, they also impact the immune system, and it depends on the given context whether this is beneficial or not. The attenuated vaccinia virus strain modified vaccinia virus Ankara (MVA) has been used as a viral vector in clinical studies intended to treat and prevent cancer and infectious diseases. The adjuvant property of MVA is thought to be due to its capability to stimulate innate immunity. Here, we confirmed that MVA induces interleukin-8 (IL-8), and this chemokine was upregulated significantly more in monocytes and HLA-DR dendritic cells (DCs) of HIV-infected patients on combined antiretroviral therapy (ART) than in cells of healthy persons. The effect of MVA on cell surface receptors is mostly unknown. Using mass cytometry profiling, we investigated the expression of 17 cell surface receptors in leukocytes after infection of human whole-blood samples with MVA. We found that MVA downregulates most of the characteristic cell surface markers in particular types of leukocytes. In contrast, C-X-C motif chemokine receptor 4 (CXCR4) was significantly upregulated in each leukocyte type of healthy persons. Additionally, we detected a relative higher cell surface expression of the HIV-1 co-receptors C-C motif chemokine receptor 5 (CCR5) and CXCR4 in leukocytes of HIV-ART patients than in healthy persons. Importantly, we showed that MVA infection significantly downregulated CCR5 in CD4+ T cells, CD8+ T cells, B cells, and three different DC populations. CD86, a costimulatory molecule for T cells, was significantly upregulated in HLA-DR DCs after MVA infection of whole blood from HIV-ART patients. However, MVA was unable to downregulate cell surface expression of CD11b and CD32 in monocytes and neutrophils of HIV-ART patients to the same extent as in monocytes and neutrophils of healthy persons. In summary, MVA modulates the expression of many different kinds of cell surface receptors in leukocytes, which can vary in cells originating from persons previously infected with other pathogens.
病毒载体越来越多地被用作诱导人类和动物特定免疫的传递手段。然而，它们也会影响免疫系统，这取决于具体情况，其影响是有益还是有害。减毒痘苗病毒株改良安卡拉痘苗病毒（MVA）已被用作临床研究中的病毒载体，旨在治疗和预防癌症和传染病。MVA 的佐剂特性被认为是由于其刺激固有免疫的能力。在这里，我们证实 MVA 诱导白细胞介素-8（IL-8），并且在接受联合抗逆转录病毒治疗（ART）的 HIV 感染患者的单核细胞和 HLA-DR 树突状细胞（DC）中，这种趋化因子的上调明显高于健康人的细胞。MVA 对细胞表面受体的影响大多未知。使用质谱细胞术分析，我们研究了 MVA 感染人全血样本后白细胞表面 17 种受体的表达。我们发现 MVA 下调了白细胞中特定类型白细胞的大多数特征性细胞表面标志物。相比之下，在健康人的每种白细胞类型中，C-X-C 基元趋化因子受体 4（CXCR4）都显著上调。此外，我们在 HIV-ART 患者的白细胞中检测到 HIV-1 共受体 C-C 基元趋化因子受体 5（CCR5）和 CXCR4 的细胞表面表达相对较高。重要的是，我们表明 MVA 感染可显著下调 CD4+T 细胞、CD8+T 细胞、B 细胞和三种不同的 DC 群体中的 CCR5。CD86 是 T 细胞的共刺激分子，在 MVA 感染来自 HIV-ART 患者的全血后的 HLA-DR DC 中显著上调。然而，MVA 不能像在健康人的单核细胞和中性粒细胞中那样，同等程度地下调 HIV-ART 患者的单核细胞和中性粒细胞中 CD11b 和 CD32 的细胞表面表达。总之，MVA 可调节白细胞中许多不同类型的细胞表面受体的表达，这些表达在来自先前感染其他病原体的患者的细胞中可能有所不同。
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