Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells
Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells
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人类粘膜肥大细胞捕获 HIV-1 并介导 CD4 T 细胞的病毒反式感染。
DOI：
10.1128/jvi.03008-15
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发表时间：
2016-03-01
影响因子：
5.4
通讯作者：
Wang, Jian-Hua
中科院分区：
文献类型：
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作者：
Jiang, Ai-Ping;Jiang, Jin-Feng;Wang, Jian-Hua
胃肠道粘膜是人类免疫缺陷病毒1型（HIV-1）侵入、扩增和持续建立的主要部位，HIV-1的细胞间传播在粘膜病毒传播中起着关键作用。肥大细胞广泛分布于胃肠道中，是侵入性病原体的早期靶点，并且已显示它们在HIV感染妇女的生殖器粘膜中具有增加的密度。肠肥大细胞表达多种病原体相关分子模式（PAMP），并已被证明可以对抗各种病毒，寄生虫和细菌感染。然而，肥大细胞在HIV-1感染中的作用尚不明确。在这项研究中，我们调查了它们对HIV-1传播的潜在贡献。发现从肠粘膜组织中分离的肥大细胞表达多种HIV-1附着因子（HAF），例如DC-SIGN、硫酸乙酰肝素蛋白聚糖（HSPG）和α 4 β 7整联蛋白，它们介导HIV-1在细胞表面的捕获。有趣的是，在与CD 4（+）T细胞共培养后，肥大细胞表面结合的病毒被有效地转移到靶T细胞。在共培养之前用抗HAF抗体或甘露聚糖阻断会损害病毒的转感染。肥大细胞和T细胞之间形成细胞-细胞连接，病毒颗粒被募集到其中，这些是HIV-1有效的细胞-细胞传播所必需的。我们的研究结果揭示了肠道粘膜肥大细胞在HIV-1在组织中传播的潜在功能。旨在防止肥大细胞介导的病毒捕获和转移的策略可能有利于对抗原发性HIV-1感染。
The gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and alpha 4 beta 7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4(+) T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viral trans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection.