Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria.
Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria.
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DOI：
10.1126/scitranslmed.add9012
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发表时间：
2023-01-25
影响因子：
17.1
通讯作者：
Jagannathan, Prasanna
中科院分区：
文献类型：
--
作者：
Ty, Maureen;Sun, Shenghuan;Callaway, Perri C.;Rek, John;Press, Kathleen D.;van der Ploeg, Kattria;Nideffer, Jason;Hu, Zicheng;Klemm, Sandy;Greenleaf, William;Donato, Michele;Tukwasibwe, Stephen;Arinaitwe, Emmanuel;Nankya, Felistas;Musinguzi, Kenneth;Andrew, Dean;de la Parte, Lauren;Mori, Diego Martinez;Lewis, Savannah N.;Takahashi, Saki;Rodriguez-Barraquer, Isabel;Greenhouse, Bryan;Blish, Catherine;Utz, P. J.;Khatri, Purvesh;Dorsey, Grant;Kamya, Moses;Boyle, Michelle;Feeney, Margaret;Ssewanyana, Isaac;Jagannathan, Prasanna
自然杀伤（NK）细胞可能在疟疾免疫中发挥重要作用，但反复疟疾对NK细胞反应的影响尚不清楚。在这里，我们全面分析了264名乌干达儿童的NK细胞反应。重复疟疾暴露与非典型cd56阴性NK细胞群的扩增有关，这些细胞在转录、表观遗传和表型上与cd56阴性NK细胞不同，包括PLZF和Fc受体γ链的表达降低，组蛋白甲基化增加，LAG-3、KIR和LILRB1的蛋白表达增加。CD56neg NK细胞比CD56dim NK细胞表现出更强的抗体依赖性细胞毒性。CD56neg NK细胞的较高频率与对症状性疟疾和高寄生虫密度的保护有关。重要的是，随着疟疾传播的显著减少，这些细胞的频率迅速下降，这表明需要持续暴露于恶性疟原虫才能维持这种修饰的、适应性样的NK细胞亚群。儿童反复罹患疟疾后，与保护免受症状性疟疾相关的功能性cd56阴性NK细胞扩增。
Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56neg population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56dim NK cells, including decreased expression of PLZF and the Fc receptor γ chain, increased histone methylation, and increased protein expression of LAG-3, KIR and LILRB1. CD56neg NK cells were highly functional and displayed greater antibody dependent cellular cytotoxicity than CD56dim NK cells. Higher frequencies of CD56neg NK cells were associated with protection against symptomatic malaria and high parasite densities. Importantly, following marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to Plasmodium falciparum is required to maintain this modified, adaptive-like NK cell subset. Repeated malaria in children is followed by expansion of functional CD56neg NK cells associated with protection from symptomatic malaria.
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AML中NK细胞改变的高维质量细胞仪分析鉴定了具有不良临床结果的亚组。
DOI：
10.1073/pnas.2020459118
发表时间：
2021-06-01
影响因子：
11.1
作者：
Chretien AS;Devillier R;Granjeaud S;Cordier C;Demerle C;Salem N;Wlosik J;Orlanducci F;Gorvel L;Fattori S;Hospital MA;Pakradouni J;Gregori E;Paul M;Rochigneux P;Pagliardini T;Morey M;Fauriat C;Dulphy N;Toubert A;Luche H;Malissen M;Blaise D;Nunès JA;Vey N;Olive D
通讯作者：
Olive D
影响因子：
6.4
作者：
Digitale, Jean C.;Callaway, Perri C.;Feeney, Margaret E.
通讯作者：
Feeney, Margaret E.
影响因子：
7.7
作者：
Cruz, Cristina;Della Rosa, Monica;Houseley, Jonathan
通讯作者：
Houseley, Jonathan
影响因子：
8
作者：
Dobbs, Katherine R.;Embury, Paula;Dent, Arlene E.
通讯作者：
Dent, Arlene E.
影响因子：
4.8
作者：
Born, TL;Thomassen, E;Sims, JE
通讯作者：
Sims, JE