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Innate Lymphoid Cell Activation and Sustained Depletion in Blood and Tissue of Children Infected with HIV from Birth Despite Antiretroviral Therapy.
Cell Reports ( IF 7.5 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.celrep.2020.108153
Alveera Singh 1 , Samuel W Kazer 2 , Julia Roider 3 , Kami C Krista 2 , Jane Millar 4 , Osaretin E Asowata 1 , Abigail Ngoepe 1 , Duran Ramsuran 1 , Rabiah Fardoos 5 , Amanda Ardain 6 , Maximilian Muenchhoff 7 , Warren Kuhn 8 , Farina Karim 1 , Thumbi Ndung'u 9 , Alex K Shalek 2 , Philip Goulder 10 , Alasdair Leslie 11 , Henrik N Kløverpris 12
Affiliation  

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.



中文翻译:

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。

先天淋巴细胞 (ILC) 对于感染反应和生命早期的免疫发育非常重要。成人感染 HIV 会消耗循环 ILC,但对出生时感染的儿童的影响仍不清楚。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 均严重且持续耗竭,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这些 ILC。其余的 ILC 上调与细胞激活和代谢扰动相关的基因。与感染艾滋病毒的成年人不同,垂直感染儿童的扁桃体中的 ILC 也严重减少。剩余 ILC 的转录谱揭示了尽管抗逆转录病毒治疗仍在持续的细胞类型特异性活性。总的来说,这些数据表明,ILC 在 HIV 感染儿童从出生起的淋巴组织中发挥着重要且持续的作用,其中持续的消耗和持续的转录活性可能会产生长期的免疫后果,值得进一步研究。

更新日期:2020-09-15
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