Differential expression of maturation and activation markers on NK cells in patients with active and latent tuberculosis
Differential expression of maturation and activation markers on NK cells in patients with active and latent tuberculosis
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DOI：
10.1002/jlb.4a1020-641rr
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发表时间：
2021-12-10
影响因子：
5.5
通讯作者：
Corbiere, Veronique
中科院分区：
文献类型：
--
作者：
Albayrak, Nurhan;Dirix, Violette;Corbiere, Veronique
最近有人认为 NK 细胞对于结核分枝杆菌感染的初始控制非常重要。使用添加到全血中的 9 种不同的 mAb，通过流式细胞术对 81 名前瞻性入组受试者（21 名未经治疗的活动性结核病患者 -aTB-、35 名潜伏性结核感染者 -LTBI- 受试者和 25 名未感染对照者）中的 3 个主要 NK 血液亚群 CD56（亮）、CD56（暗）和 CD56（阴性）细胞的表型进行了表征。与 LTBI 受试者相比，aTB 患者的 NK 细胞总数较低，表达早期成熟标志物（CD161、NKp30、NKp46）的 CD56(neg) 细胞比例和数量较低，但 CD56(neg) 和 CD56(dim) 亚群的 NKp30 和 NKp46 表达密度较高，与颗粒酶 A/B 的较高表达相关。在所有 3 个 NK 细胞亚群中，它们的活化 CD69(pos) 细胞比例也较高，并且 CD69(pos) 和/或 NKG2C(pos) NK 细胞中 CD69(pos) CD56(dim) 细胞的百分比被确定为区分 aTB 和 LTBI 的潜在生物标志物。相反，与 aTB 患者相比，LTBI 受试者的特征是 CD56(neg) 亚群上晚期成熟标志物（CD57、KIR 分子）表达较高、NKG2C(pos)KIR(pos) CD56(dim) NK 细胞比例较高以及体外 IFN-γ 产生较高。因此，血液 NK 细胞亚群的深入表型特征为 NK 细胞可能的功能修饰以及 NK 细胞在控制人类结核分枝杆菌感染中的潜在作用提供了新的见解。
NK cells were recently suggested to be important for the initial control of M. tuberculosis infection. The phenotypes of the 3 main NK blood subsets, CD56(bright), CD56(dim), and CD56(neg) cells, were characterized by flow cytometry in a cohort of 81 prospectively enrolled subjects (21 untreated patients with active tuberculosis -aTB-, 35 latently TB infected -LTBI- subjects, and 25 non-infected controls), using 9 different mAbs added to whole blood. Compared to LTBI subjects, patients with aTB had lower proportions of total NK cells, lower proportions and numbers of CD56(neg) cells expressing early maturation markers (CD161, NKp30, NKp46), but higher density of NKp30 and NKp46 expression on both CD56(neg) and CD56(dim) subsets, associated with higher expression of granzymes A/B. They also had higher proportions of activated CD69(pos) cells within all 3 NK cell subsets and, the percentage of CD69(pos) CD56(dim) cells among CD69(pos) and/or NKG2C(pos) NK cells was identified as a potential biomarker to discriminate aTB from LTBI. LTBI subjects were in contrast characterized by higher expression of late maturation markers (CD57, KIR molecules) on the CD56(neg) subset, by higher proportions of NKG2C(pos)KIR(pos) CD56(dim) NK cells, and by higher in vitro IFN-gamma production than patients with aTB. Thus, the in-depth phenotypic characterization of blood NK cell subsets provides new insights on possible functional modifications and the potential role of NK cells in the control of M. tuberculosis infection in humans.