Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys.
Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys.
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DOI：
10.1038/nm.4421
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发表时间：
2017-11
期刊：
影响因子：
82.9
通讯作者：
Müller-Trutwin M
中科院分区：
文献类型：
--
作者：
Huot N;Jacquelin B;Garcia-Tellez T;Rascle P;Ploquin MJ;Madec Y;Reeves RK;Derreudre-Bosquet N;Müller-Trutwin M
自然杀伤（NK）细胞在抗病毒免疫中发挥重要作用，但对它们在次级淋巴器官中的功能的了解尚不完整。淋巴结滤泡是HIV-1和猴免疫缺陷病毒（SIVmac）感染过程中的主要病毒库。相反，在非致病性感染SIV从非洲绿色猴（SIVagm），卵泡通常保持无病毒。我们发现慢性SIVagm感染的非洲绿色猴（AGM）次级淋巴器官中的NK细胞经常是CXCR 5+，并在整个随访期间（感染后240天）进入并持续存在于淋巴结滤泡中。这些滤泡对IL-15呈强阳性，IL-15主要以其膜结合形式由滤泡树突状细胞呈递。在慢性SIVagm感染期间通过抗IL-15单克隆抗体治疗的NK细胞耗竭导致卵泡和T细胞区中的高病毒复制率以及淋巴结中的病毒DNA增加。我们的数据表明，在非致病性SIV感染中，NK细胞迁移到滤泡中，并在淋巴结中的病毒储库控制中发挥重要作用。
Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodeficiency virus of macaques (SIVmac). In contrast, during nonpathogenic infection with SIV from African green monkeys (SIVagm), follicles remain generally virus free. We show that NK cells in secondary lymphoid organs from chronically SIVagm-infected African green monkeys (AGMs) were frequently CXCR5+ and entered and persisted in lymph node follicles throughout the follow-up (240 d post-infection). These follicles were strongly positive for IL-15, which was primarily presented in its membrane-bound form by follicular dendritic cells. NK cell depletion through treatment with anti-IL-15 monoclonal antibody during chronic SIVagm infection resulted in high viral replication rates in follicles and the T cell zone and increased viral DNA in lymph nodes. Our data suggest that, in nonpathogenic SIV infection, NK cells migrate into follicles and play a major role in viral reservoir control in lymph nodes.
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