牛磺酸通过调节伯氏疟原虫感染小鼠的免疫反应增强青蒿素抗疟疾的功效。

IF 3.5 2区 医学 Q1 PARASITOLOGY Parasites & Vectors Pub Date : 2024-11-29 DOI:10.1186/s13071-024-06585-y
Xin Li, Ning Jiang, Qilong Li, Kexin Zheng, Yiwei Zhang, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen
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引用次数: 0

摘要

背景:青蒿素(ART)是治疗疟疾的一线药物;然而,抗逆转录病毒药物耐药性疟原虫菌株的出现需要提高抗逆转录病毒药物的敏感性。鉴于牛磺酸(TAU)已被证明具有免疫调节活性,我们研究了TAU作为感染伯氏疟原虫的小鼠抗逆转录病毒治疗的辅助疗法的效果。方法:分别用TAU单用、ART单用或TAU联合ART (TAU + ART)治疗感染伯氏勃氏杆菌ANKA株的小鼠,记录其生存时间和寄生率。随后评估TAU和ART的细胞毒性作用。分析感染伯氏单胞菌ANKA小鼠中炎性小体相关基因和炎症因子的表达水平与单独使用TAU、单独使用ART或TAU + ART联合治疗小鼠的表达水平的关系。通过组织学分析和脾指数测定进一步评价治疗效果。结果:与对照组小鼠相比,ART联合TAU治疗伯氏线虫anka感染小鼠的寄生虫率明显降低,生存期延长。联合治疗导致脾脏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)、caspase-1、NOD-、LRR-和pyrin结构域蛋白3 (Nlrp3)、Nlrp1b、Nlrp1b、NLR家族CARD结构域4 (Nlrc4)、Nlrp6、核苷酸结合寡聚结构域1 (NOD1)和NOD2,血清中炎症细胞因子水平降低,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联合治疗可减轻伯氏弧菌ANKA感染引起的脾脏病理。结论:这些发现表明TAU通过调节伯氏杆菌感染小鼠的免疫反应来增强抗逆转录病毒治疗的疗效。
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Taurine potentiates artemisinin efficacy against malaria by modulating the immune response in Plasmodium berghei-infected mice.

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.

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来源期刊
Parasites & Vectors
Parasites & Vectors 医学-寄生虫学
CiteScore
6.30
自引率
9.40%
发文量
433
审稿时长
1.4 months
期刊介绍: Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish. Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.
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