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人淋巴细胞亚群的麻疹病毒感染显示出初始B细胞和记忆B细胞均具有高易感性和允许性。

Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells.

作者信息

Laksono Brigitta M, Grosserichter-Wagener Christina, de Vries Rory D, Langeveld Simone A G, Brem Maarten D, van Dongen Jacques J M, Katsikis Peter D, Koopmans Marion P G, van Zelm Menno C, de Swart Rik L

机构信息

Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands.

Department of Immunology, Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands.

出版信息

J Virol. 2018 Mar 28;92(8). doi: 10.1128/JVI.00131-18. Print 2018 Apr 15.

Abstract

Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (T) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that T1T17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cells However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness to MV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance.

摘要

麻疹的特征是短暂的免疫抑制,导致机会性感染风险增加。免疫细胞的麻疹病毒(MV)感染由细胞受体CD150介导,CD150由淋巴细胞、树突状细胞、巨噬细胞和胸腺细胞亚群表达。先前的研究表明,人类和非人类灵长类动物的记忆T细胞比幼稚细胞表达更高水平的CD150,并且更容易受到MV感染。然而,关于B细胞亚群的CD150表达及其对MV感染的相对易感性的信息有限。在本研究中,我们评估了来自人外周血或扁桃体的幼稚和记忆T细胞及B细胞亚群对MV感染的易感性和允许性。我们的研究表明,幼稚和记忆B细胞表达CD150,但频率低于记忆T细胞。然而,幼稚和记忆B细胞均被证明对MV感染高度易感。此外,我们评估了外周血和扁桃体中各种功能不同的T细胞和B细胞的易感性和允许性,如辅助性T(Th)细胞亚群以及IgG和IgA阳性记忆B细胞。我们证明T1Th17细胞以及浆细胞和生发中心B细胞是最易受MV感染且对其易感的亚群。我们的研究表明,幼稚和记忆B细胞以及其他几种经历过抗原刺激的淋巴细胞都是MV感染的重要靶细胞。这些细胞的耗竭可能导致麻疹免疫抑制的发病机制。麻疹与免疫抑制相关,常并发细菌性肺炎、中耳炎或肠胃炎。麻疹病毒感染抗原呈递细胞以及T细胞和B细胞,这些细胞的耗竭可能导致淋巴细胞减少和免疫抑制。麻疹与人类和非人类灵长类动物淋巴组织中的滤泡耗竭有关,强调了MV感染B细胞的重要性。然而,关于B细胞亚群相对易感性的信息很少。在这里,我们比较了从外周血或扁桃体中分离出的人类幼稚和记忆T细胞及B细胞亚群对MV感染的易感性和允许性。我们的结果表明,幼稚和记忆B细胞比T细胞对MV感染更易感。在浆细胞和生发中心B细胞中检测到最高感染水平,这表明这些细胞群的感染和耗竭导致宿主抵抗力下降。

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