Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Eur J Immunol. 2011 Sep;41(9):2619-31. doi: 10.1002/eji.201041305. Epub 2011 Aug 8.
Langerhans cells (LCs) are a subset of DCs that reside in the upper respiratory tract and are ideally suited to sense respiratory virus infections. Measles virus (MV) is a highly infectious lymphotropic and myelotropic virus that enters the host via the respiratory tract. Here, we show that human primary LCs are capable of capturing MV through the C-type lectin Langerin. Both immature and mature LCs presented MV-derived antigens in the context of HLA class II to MV-specific CD4(+) T cells. Immature LCs were not susceptible to productive infection by MV and did not present endogenous viral antigens in the context of HLA class I. In contrast, mature LCs could be infected by MV and presented de novo synthesized viral antigens to MV-specific CD8(+) T cells. Notably, neither immature nor mature LCs were able to cross-present exogenous UV-inactivated MV or MV-infected apoptotic cells. The lack of direct infection of immature LCs, and the inability of both immature and mature LCs to cross-present MV antigens, suggest that human LCs may not be directly involved in priming MV-specific CD8(+) T cells. Immune activation of LCs seems a prerequisite for MV infection of LCs and subsequent CD8(+) T-cell priming via the endogenous antigen presentation pathway.
朗格汉斯细胞(LCs)是 DCs 的一个亚群,存在于上呼吸道,非常适合感知呼吸道病毒感染。麻疹病毒(MV)是一种高度传染性的淋巴嗜性和骨髓嗜性病毒,通过呼吸道进入宿主。在这里,我们表明人原代 LCs 能够通过 C 型凝集素 Langerin 捕获 MV。未成熟和成熟的 LCs 在 HLA Ⅱ类的背景下呈现 MV 衍生的抗原,以刺激 MV 特异性 CD4+T 细胞。未成熟的 LCs 不易被 MV 产生性感染,并且不在 HLA Ⅰ类的背景下呈现内源性病毒抗原。相比之下,成熟的 LCs 可以被 MV 感染,并将新合成的病毒抗原呈递给 MV 特异性 CD8+T 细胞。值得注意的是,未成熟和成熟的 LCs 均不能交叉呈递外源性 UV 灭活的 MV 或感染凋亡细胞的 MV。未成熟 LCs 不能直接感染,以及未成熟和成熟 LCs 均不能交叉呈递 MV 抗原,表明人类 LCs 可能不直接参与刺激 MV 特异性 CD8+T 细胞。LCs 的免疫激活似乎是 LCs 感染 MV 和随后通过内源性抗原呈递途径诱导 CD8+T 细胞的先决条件。