牛磺酸通过调节感染伯氏疟原虫小鼠的免疫应答增强青蒿素的抗疟疗效。

Taurine potentiates artemisinin efficacy against malaria by modulating the immune response in Plasmodium berghei-infected mice.

机构信息

Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang, 110866, China.

Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866, China.

出版信息

Parasit Vectors. 2024 Nov 29;17(1):493. doi: 10.1186/s13071-024-06585-y.

DOI:10.1186/s13071-024-06585-y

PMID:39614280

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11606117/

Abstract

BACKGROUND

Artemisinin (ART) is a frontline drug for the treatment of malaria; however, the emergence of ART-resistant Plasmodium strains necessitates increasing ART sensitivity. Given that taurine (TAU) has been shown to have immunomodulatory activity, we investigated the effects of TAU as an adjunct therapy to ART in mice infected with Plasmodium berghei.

METHODS

Mice infected with P. berghei ANKA strain (P. berghei ANKA) were treated with TAU alone, ART alone or a combination of TAU and ART (TAU + ART), and their survival time and parasitaemia were recorded. The cytotoxic effects of TAU and ART were subsequently assessed. The expression levels of inflammasome-related genes and inflammatory factors in mice infected with P. berghei ANKA were analysed in relation to those in mice treated with TAU alone, ART alone or the TAU + ART combination. The therapeutic effects were further evaluated by histological analysis and measurement of the spleen index.

RESULTS

Compared with the control mice, P. berghei ANKA-infected mice treated with ART in combination with TAU presented significantly lower parasitaemia and prolonged survival. The combined treatment resulted in significant reductions in the expression levels of inflammasome-related genes in the spleen, including absent in melanoma 2 (AIM2), caspase-1, NOD-, LRR- and pyrin domain-containing protein 3 (Nlrp3), Nlrp1b, Nlrp1b, NLR family CARD domain containing 4 (Nlrc4), Nlrp6, nucleotide binding oligomerization domain containing 1 (NOD1) and NOD2, and decreases in the levels of inflammatory cytokines in the serum, including interleukin (IL)-12p70, tumour necrosis factor-alpha, monocyte chemoattractant protein-1, IL-10 and IL-6. Histopathological analysis confirmed that TAU + ART combination treatment reduced spleen pathology caused by P. berghei ANKA infection.

CONCLUSIONS

The findings indicate that TAU potentiates ART efficacy by modulating the immune response in P. berghei-infected mice.

摘要

背景

青蒿素（ART）是治疗疟疾的一线药物；然而，青蒿素耐药疟原虫株的出现需要提高青蒿素的敏感性。鉴于牛磺酸（TAU）已被证明具有免疫调节活性，我们研究了 TAU 作为辅助治疗药物在感染伯氏疟原虫的小鼠中的作用。

方法

用伯氏疟原虫 ANKA 株（P. berghei ANKA）感染的小鼠单独用 TAU、ART 或 TAU 和 ART（TAU + ART）联合治疗，并记录其存活时间和寄生虫血症。随后评估 TAU 和 ART 的细胞毒性作用。分析感染伯氏疟原虫 ANKA 的小鼠的炎症小体相关基因和炎症因子的表达水平与单独用 TAU、ART 或 TAU + ART 联合治疗的小鼠的表达水平。通过组织学分析和脾指数测量进一步评估治疗效果。

结果

与对照组相比，用 ART 联合 TAU 治疗的感染伯氏疟原虫的小鼠寄生虫血症显著降低，存活时间延长。联合治疗导致脾中炎症小体相关基因的表达水平显著降低，包括黑色素瘤 2（AIM2）、半胱氨酸天冬氨酸蛋白酶-1（caspase-1）、NOD-、LRR-和吡喃域包含蛋白 3（Nlrp3）、Nlrp1b、Nlrp1b、NLR 家族 CARD 域包含 4（Nlrc4）、Nlrp6、核苷酸结合寡聚化结构域包含 1（NOD1）和 NOD2，以及血清中炎症细胞因子的水平降低，包括白细胞介素（IL）-12p70、肿瘤坏死因子-α、单核细胞趋化蛋白-1、IL-10 和 IL-6。组织病理学分析证实，TAU + ART 联合治疗可减轻由伯氏疟原虫 ANKA 感染引起的脾病理变化。