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在暴露于镰状细胞性状的患病儿童中，与低寄生虫血症相关的新型记忆激活自然杀伤细胞群体。

A novel population of memory-activated natural killer cells associated with low parasitaemia in -exposed sickle-cell trait children.

作者信息

Loiseau Claire, Doumbo Ogobara K, Traore Boubacar, Brady Jamie L, Proietti Carla, de Sousa Karina P, Crompton Peter D, Doolan Denise L

机构信息

Centre for Molecular Therapeutics Australian Institute of Tropical Health & Medicine James Cook University Cairns QLD Australia.

Mali International Center of Excellence in Research University of Sciences, Technique and Technology of Bamako Bamako Mali.

出版信息

Clin Transl Immunology. 2020 Apr 2;9(4):e1125. doi: 10.1002/cti2.1125. eCollection 2020 Apr.

DOI:10.1002/cti2.1125
PMID:32257211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7114700/
Abstract

OBJECTIVES

The sickle-cell trait phenotype is associated with protection from malaria. Multiple molecular mechanisms have been proposed to explain this protection, but the role of the host immune system has been poorly investigated. We hypothesised that cellular immunity to malaria may develop differently in sickle-cell trait children (HbAS) and children with normal haemoglobin (HbAA) repeatedly exposed to ().

METHODS

Paired samples collected prior to the transmission season and during the first malaria episode of the ensuing transmission season from HbAS and HbAA children were analysed by multiplex bead-based assay and comprehensive multi-dimensional flow cytometry profiling.

RESULTS

Cellular immune profiles were enriched in HbAS relative to HbAA children before the start of the transmission season, with a distinct NK subset. These cells were identified as a novel subset of memory-activated NK cells characterised by reduced expression of the ecto-enzyme CD38 as well as co-expression of high levels of HLA-DR and CD45RO. The frequency of this NK subset before the transmission season was negatively correlated with parasite density quantified during the first malaria episode of the ensuing transmission season. Functional assessment revealed that these CD38 CD45RO HLA-DR NK cells represent a important source of IFN-γ.

CONCLUSION

Our data suggest that this novel memory-activated NK cell subset may contribute to an accelerated and enhanced IFN-γ-mediated immune response and to control of parasite density in individuals with the sickle-cell trait. This distinct cellular immune profile may contribute to predispose HbAS children to a relative protection from malaria.

摘要

目的

镰状细胞性状表型与预防疟疾有关。已提出多种分子机制来解释这种保护作用，但宿主免疫系统的作用尚未得到充分研究。我们假设，反复接触（）的镰状细胞性状儿童（HbAS）和正常血红蛋白儿童（HbAA）对疟疾的细胞免疫可能会有不同的发展。

方法

通过基于微珠的多重检测和全面的多维流式细胞术分析，对在传播季节开始前以及随后传播季节的首次疟疾发作期间从HbAS和HbAA儿童收集的配对样本进行分析。

结果

在传播季节开始前，相对于HbAA儿童，HbAS儿童的细胞免疫谱有所富集，有一个独特的自然杀伤细胞（NK）亚群。这些细胞被鉴定为记忆激活型NK细胞的一个新亚群，其特征是胞外酶CD38表达降低以及高水平的人类白细胞抗原-DR（HLA-DR）和CD45RO共表达。传播季节前这个NK亚群的频率与随后传播季节首次疟疾发作期间量化的寄生虫密度呈负相关。功能评估显示，这些CD38-CD45RO-HLA-DR NK细胞是γ干扰素（IFN-γ）的一个重要来源。

结论

我们的数据表明，这个新的记忆激活型NK细胞亚群可能有助于加速和增强IFN-γ介导的免疫反应，并有助于控制镰状细胞性状个体中的寄生虫密度。这种独特的细胞免疫谱可能有助于使HbAS儿童相对预防疟疾。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b969/7114700/58d57b7fd8a1/CTI2-9-e1125-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b969/7114700/bfff48b18041/CTI2-9-e1125-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b969/7114700/58d57b7fd8a1/CTI2-9-e1125-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b969/7114700/2d762e98d91a/CTI2-9-e1125-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b969/7114700/58d57b7fd8a1/CTI2-9-e1125-g007.jpg

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