Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway.
Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway.
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HIV 通过 1 型干扰素途径感染和消耗 CD4 1 族 ILC
DOI：
10.1371/journal.ppat.1006819
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发表时间：
2018-01
期刊：
影响因子：
6.7
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Zhao J;Cheng L;Wang H;Yu H;Tu B;Fu Q;Li G;Wang Q;Sun Y;Zhang X;Liu Z;Chen W;Zhang L;Su L;Zhang Z
在慢性 HIV-1 感染过程中，固有淋巴细胞 (ILC) 严重耗竭，但机制尚不清楚。我们在此报道，由 CD4+ 和 CD4- 亚群组成的人类 ILC1 存在于各种人类淋巴器官中，但具有不同的转录程序和功能。重要的是，CD4+ ILC1 表达 HIV-1 共受体，并在体外和体内有效地被 HIV-1 感染。此外，慢性HIV-1感染激活并耗尽了CD4+和CD4-ILC1，并损害了它们的细胞因子产生活性。 HIV-1患者的高效抗逆转录病毒（HAART）疗法有效地挽救了ILC1数量并减少了它们的激活，但未能恢复它们的功能。我们还发现，在人源化小鼠体内 HIV-1 感染期间阻断 I 型干扰素 (IFN-I) 信号传导可防止 HIV-1 诱导的 ILC1 细胞耗竭或凋亡。因此，我们将CD4+ ILC1细胞确定为HIV-1感染的新目标群体，并揭示IFN-I有助于HIV-1感染期间ILC1的消耗。先天淋巴细胞 (ILC)，包括 ILC1、ILC2 和 ILC3 群体，代表免疫系统的一个新细胞家族，在没有特定抗原刺激的情况下，有可能响应先天刺激而产生大量 T 细胞相关细胞因子。 ILC 已成为稳态和炎症条件下的核心参与者，并与多种人类疾病的发病机制和进展相关。据报道，HIV-1 感染患者的 ILC 已耗尽。然而，尚不清楚 HIV-1 是否可以感染 ILC 以及 ILC 在 HIV-1 感染期间如何耗尽。在这里，我们发现 ILC1 由 CD4+ 和 CD4- 亚群组成，两者都存在于各种人类淋巴器官中。我们证明 HIV-1 可以直接感染 CD4+ ILC1。 HIV-1 感染会导致人类和人源化小鼠体内 ILC1 的激活、耗竭和功能损伤。阻断 IFN-I 信号传导可防止 HIV-1 诱导的 ILC1 细胞凋亡，无论是体外还是人源化小鼠体内。我们的研究揭示了 CD4+ ILC1 群体是 HIV-1 感染的新目标，并确定了慢性 HIV-1 感染期间 IFN-I 介导的 ILC1 耗竭机制。
Innate lymphoid cells (ILCs) are severely depleted during chronic HIV-1 infection by unclear mechanisms. We report here that human ILC1s comprising of CD4+ and CD4- subpopulations were present in various human lymphoid organs but with different transcription programs and functions. Importantly, CD4+ ILC1s expressed HIV-1 co-receptors and were productively infected by HIV-1 in vitro and in vivo. Furthermore, chronic HIV-1 infection activated and depleted both CD4+ and CD4- ILC1s, and impaired their cytokine production activity. Highly active antiretroviral (HAART) therapy in HIV-1 patients efficiently rescued the ILC1 numbers and reduced their activation, but failed to restore their functionality. We also found that blocking type-I interferon (IFN-I) signaling during HIV-1 infection in vivo in humanized mice prevented HIV-1 induced depletion or apoptosis of ILC1 cells. Therefore, we have identified the CD4+ ILC1 cells as a new target population for HIV-1 infection, and revealed that IFN-I contributes to the depletion of ILC1s during HIV-1 infection. Innate lymphoid cells (ILCs), including ILC1, ILC2 and ILC3 populations, represent a novel cellular family of the immune system and have potentials to produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of specific antigen stimulation. ILCs have emerged as central players in homeostatic and inflammatory conditions, and correlated with the pathogenesis and progression of multiple human diseases. It is reported that ILCs are depleted in HIV-1 infected patients. However, it is not clear whether HIV-1 can infect ILCs and how ILCs are depleted during HIV-1 infection. Here, we find that ILC1s consist CD4+ and CD4- subsets and both are present in various human lymphoid organs. We show that HIV-1 can directly infect CD4+ ILC1s. HIV-1 infection leads to activation, depletion and functional impairment of ILC1s in humans and in humanized mice in vivo. Blocking IFN-I signaling prevents HIV-1-induced apoptosis of ILC1s both in vitro and in humanized mice in vivo. Our study reveals the CD4+ ILC1 population as a new target for HIV-1 infection and identifies an IFN-I mediated mechanism of ILC1 depletion during chronic HIV-1 infection.
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人类先天淋巴细胞冗余的证据。
影响因子：
30.5
作者：
通讯作者：
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影响因子：
8
作者：
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通讯作者：
Su, Lishan
影响因子：
32.4
作者：
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通讯作者：
Spits, Hergen
影响因子：
32.4
作者：
Sonnenberg, Gregory F;Mjosberg, Jenny;Artis, David
通讯作者：
Artis, David
影响因子：
30.5
作者：
Bernink, Jochem H.;Peters, Charlotte P.;Spits, Hergen
通讯作者：
Spits, Hergen