Role for Plasmacytoid Dendritic Cells in the Immune Control of Recurrent Human Herpes Simplex Virus Infection

Role for Plasmacytoid Dendritic Cells in the Immune Control of Recurrent Human Herpes Simplex Virus Infection
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DOI:
10.1128/jvi.01578-08
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发表时间:
2009-02-15
影响因子:
5.4
通讯作者:
Cunningham, Anthony L.
Cunningham, Anthony L.
中科院分区:
医学2区
文献类型:
--
作者:
Donaghy, Heather;Bosnjak, Lidija;Cunningham, Anthony L.

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浆细胞样树突状细胞(pDC)是先天免疫反应的重要组成部分,在体外对病毒刺激产生大量α干扰素。在非炎症条件下,pDC不在皮肤中发现,仅限于血液和淋巴结的位置。因此,它们在粘膜和皮肤单纯疱疹病毒(HSV)感染中的作用尚未明确。在这项研究中,我们展示了人类pDC在HSV感染的免疫反应中的作用。首先,通过共聚焦显微镜,我们发现pDC在复发性生殖器单纯疱疹病变的早期和晚期浸润真皮,通常在真皮-表皮交界处。我们随后发现,尽管pDC在体外表达了进入受体CD111、CD112和HVE-A,但它对HSV感染具有抗性。在病变内,pDC与CD3(+)淋巴细胞和NK细胞密切相关,尤其是活化的CD69(+)淋巴细胞。此外,这些暴露于hsv的pDC能够刺激病毒特异性的自体t淋巴细胞增殖。我们由此得出结论,pDC可能有助于体内复发性疱疹病毒感染的免疫控制。
Plasmacytoid dendritic cells (pDC) are an important component of the innate immune response, producing large amounts of alpha interferon in response to viral stimulation in vitro. Under noninflammatory conditions, pDC are not found in the skin and are restricted in location to the blood and lymph nodes. Therefore, their role in mucosal and cutaneous herpes simplex virus (HSV) infection has not been well-defined. In this study we show a role for human pDC in the immune response to HSV infection. First, by confocal microscopy we showed that pDC infiltrate the dermis of recurrent genital herpes simplex lesions at early and late phases, often at the dermo-epidermal junction. We then showed that pDC in vitro are resistant to HSV infection despite expressing the entry receptors CD111, CD112, and HVE-A. Within the lesions, pDC were found closely associated with CD3(+) lymphocytes and NK cells, especially those which were activated (CD69(+)). Furthermore, these HSV-exposed pDC were able to stimulate virus-specific autologous T-lymphocyte proliferation. We conclude from this work that pDC may contribute to the immune control of recurrent herpes virus infection in vivo.