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季节性疟疾化学预防对衰竭和调节免疫标志物的影响。

Effect of Seasonal Malaria Chemoprevention on Immune Markers of Exhaustion and Regulation.

机构信息

Malaria Research and Training Center, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.

Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

出版信息

J Infect Dis. 2020 Jan 1;221(1):138-145. doi: 10.1093/infdis/jiz415.

Abstract

BACKGROUND

Seasonal malaria chemoprevention (SMC) is a novel strategy to reduce malaria infections in children. Infection with Plasmodium falciparum results in immune dysfunction characterized by elevated expression of markers associated with exhaustion, such as PD1 and LAG3, and regulatory CD4+FOXP3+ T cells.

METHODS

In the current study, the impact of seasonal malaria chemoprevention on malaria-induced immune dysfunction, as measured by markers associated with exhaustion and regulatory T cells, was explored by flow cytometry.

RESULTS

Children that received seasonal malaria chemoprevention had fewer malaria episodes and showed significantly lower fold changes in CD4+PD1+ and CD4+PD1+LAG3+ compared to those that did not receive SMC. Seasonal malaria chemoprevention had no observable effect on fold changes in CD8 T cells expressing PD1 or CD160. However, children receiving SMC showed greater increases in CD4+FOXP3+ T regulatory cells compared to children not receiving SMC.

CONCLUSIONS

These results provide important insights into the dynamics of malaria-induced changes in the CD4 T-cell compartment of the immune system and suggest that the reduction of infections due to seasonal malaria chemoprevention may also prevent immune dysfunction.

CLINICAL TRIALS REGISTRATION

NCT02504918.

摘要

背景

季节性疟疾化学预防(SMC)是一种减少儿童疟疾感染的新策略。感染疟原虫会导致免疫功能障碍,表现为与衰竭相关的标志物表达升高,如 PD1 和 LAG3,以及调节性 CD4+FOXP3+T 细胞。

方法

在本研究中,通过流式细胞术探讨了季节性疟疾化学预防对疟疾引起的免疫功能障碍的影响,这些标志物与衰竭和调节性 T 细胞有关。

结果

接受季节性疟疾化学预防的儿童疟疾发作次数较少,与未接受 SMC 的儿童相比,CD4+PD1+和 CD4+PD1+LAG3+的倍数变化明显较低。季节性疟疾化学预防对表达 PD1 或 CD160 的 CD8 T 细胞的倍数变化没有明显影响。然而,接受 SMC 的儿童的 CD4+FOXP3+T 调节性细胞增加幅度大于未接受 SMC 的儿童。

结论

这些结果提供了关于疟疾引起的免疫系统 CD4 T 细胞区室变化动态的重要见解,并表明季节性疟疾化学预防减少感染也可能预防免疫功能障碍。

临床试验注册

NCT02504918。

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