Benznidazole treatment decreases IL-6 levels in Trypanosoma cruzi-infected human adipocytes differentiated from adipose tissue-derived stem cells.

IF 2.5 4区 医学 Q2 PARASITOLOGY Memorias do Instituto Oswaldo Cruz Pub Date : 2023-10-23 eCollection Date: 2023-01-01 DOI:10.1590/0074-02760220295
Leyllane Rafael Moreira, Ana Carla Silva, Cíntia Nascimento da Costa Oliveira, Claudeir Dias da Silva Júnior, Amanda Vasconcelos Nascimento, Kamila Kássia Dos Santos Oliveira, Ana Karine de Araújo Soares, Karina Lidianne Alcântara Saraiva, Milena de Paiva Cavalcanti, Virginia Maria Barros de Lorena
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Abstract

Background: Trypanosoma cruzi, which causes Chagas disease (CD), is a versatile haemoparasite that uses several strategies to evade the host's immune response, including adipose tissue (AT), used as a reservoir of infection. As it is an effective barrier to parasite evasion, the effectiveness of the drug recommended for treating CD, Benznidazole (BZ), may be questionable.

Objective: To this end, we evaluated the parasite load and immunomodulation caused by BZ treatment in the culture of adipocytes differentiated from human adipose tissue-derived stem cells (ADSC) infected with T. cruzi.

Methods: The ADSC were subjected to adipogenic differentiation. We then carried out four cultures in which we infected the differentiated AT with trypomastigote forms of the Y strain of T. cruzi and treated them with BZ. After the incubation, the infected AT was subjected to quantitative polymerase chain reaction (qPCR) to quantify the parasite load and transmission electron microscopy (TEM) to verify the infection. The supernatant was collected to measure cytokines, chemokines, and adipokines.

Findings: We found elevated secretion of IL-6, CXCL-10/IP-10, CCL2/MCP-1, CCL5/RANTES, and leptin in infected fat cells. However, treatment with BZ promoted a decrease in IL-6.

Main conclusion: Therefore, we believe that BZ has a beneficial role as it reduces inflammation in infected fat cells.

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苯硝唑治疗降低了从脂肪组织衍生的干细胞分化的感染克氏锥虫的人类脂肪细胞中的IL-6水平。
背景:引起恰加斯病(CD)的克氏锥虫是一种多功能的血寄生虫,它使用多种策略来逃避宿主的免疫反应,包括用作感染宿主的脂肪组织(AT)。由于它是寄生虫逃避的有效屏障,推荐用于治疗CD的药物苄唑(BZ)的有效性可能值得怀疑。目的:为了达到这个目的,我们评估BZ处理在从感染克氏锥虫的人脂肪组织衍生干细胞(ADSC)分化的脂肪细胞培养中引起的寄生虫负荷和免疫调节。方法:对ADSC进行成脂分化。然后,我们进行了四种培养,用克鲁兹锥虫Y株的锥虫体形式感染分化的AT,并用BZ处理它们。培养后,对感染的AT进行定量聚合酶链式反应(qPCR)以量化寄生虫载量,并用透射电子显微镜(TEM)验证感染。收集上清液以测量细胞因子、趋化因子和脂肪因子。研究结果:我们发现受感染的脂肪细胞中IL-6、CXCL-10/IP-10、CCL2/MCP-1、CCL5/RANTES和瘦素的分泌增加。然而,BZ治疗促进了IL-6的降低。主要结论:因此,我们认为BZ具有有益的作用,因为它可以减少感染脂肪细胞的炎症。
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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
91
审稿时长
3-8 weeks
期刊介绍: Memórias do Instituto Oswaldo Cruz is a journal specialized in microbes & their vectors causing human infections. This means that we accept manuscripts covering multidisciplinary approaches and findings in the basic aspects of infectious diseases, e.g. basic in research in prokariotes, eukaryotes, and/or virus. Articles must clearly show what is the main question to be answered, the hypothesis raised, and the contribution given by the study. Priority is given to manuscripts reporting novel mechanisms and general findings concerning the biology of human infectious prokariotes, eukariotes or virus. Papers reporting innovative methods for diagnostics or that advance the basic research with these infectious agents are also welcome. It is important to mention what we do not publish: veterinary infectious agents research, taxonomic analysis and re-description of species, epidemiological studies or surveys or case reports and data re-analysis. Manuscripts that fall in these cases or that are considered of low priority by the journal editorial board, will be returned to the author(s) for submission to another journal.
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