Innate Lymphoid Cell Activation and Sustained Depletion in Blood and Tissue of Children Infected with HIV from Birth Despite Antiretroviral Therapy.
Innate Lymphoid Cell Activation and Sustained Depletion in Blood and Tissue of Children Infected with HIV from Birth Despite Antiretroviral Therapy.
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尽管接受抗逆转录病毒治疗，但出生后感染艾滋病毒的儿童的血液和组织中的先天淋巴细胞激活和持续耗竭。
DOI：
10.1016/j.celrep.2020.108153
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发表时间：
2020
期刊：
影响因子：
8.8
通讯作者：
Gou
中科院分区：
文献类型：
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作者：
Singh,Alveera;Kazer,SamuelW;Roider,Julia;Krista,KamiC;Millar,Jane;Asowata,OsaretinE;Ngoepe,Abigail;Ramsuran,Duran;Fardoos,Rabiah;Ardain,Amanda;Muenchhoff,Maximilian;Kuhn,Warren;Karim,Farina;Ndung'u,Thumbi;Shalek,AlexK;Gou
先天性淋巴样细胞（ILC）对于早期生命中对感染的反应和免疫发育是重要的。成人感染艾滋病毒会耗尽循环中的ILC，但对出生时感染的儿童的影响仍然未知。我们研究了从出生到成年的垂直HIV感染儿童，发现所有循环ILC的严重和持续消耗，与CD4+T细胞不同，除非在出生时开始，否则长期抗逆转录病毒治疗不会恢复。剩余的ILC上调与细胞活化和代谢扰动相关的基因。与感染艾滋病毒的成人不同，ILC在垂直感染儿童的扁桃体中也严重耗竭。剩余ILC的转录谱显示尽管抗逆转录病毒治疗仍存在细胞类型特异性活性。总的来说，这些数据表明一个重要的和持续的作用ILC在淋巴组织的HIV感染的儿童从出生，持续消耗和持续的转录活性可能有长期的免疫后果，值得进一步研究。
Innate lymphoid cells (ILCs) are important for response to infection and for immune development in early life. HIV infection in adults depletes circulating ILCs, but the impact on children infected from birth remains unknown. We study vertically HIV-infected children from birth to adulthood and find severe and persistent depletion of all circulating ILCs that, unlike CD4+T cells, are not restored by long-term antiretroviral therapy unless initiated at birth. Remaining ILCs upregulate genes associated with cellular activation and metabolic perturbation. Unlike HIV-infected adults, ILCs are also profoundly depleted in tonsils of vertically infected children. Transcriptional profiling of remaining ILCs reveals ongoing cell-type-specific activity despite antiretroviral therapy. Collectively, these data suggest an important and ongoing role for ILCs in lymphoid tissue of HIV-infected children from birth, where persistent depletion and sustained transcriptional activity are likely to have long-term immune consequences that merit further investigation.