MicroRNA mmu-miR-511-5p: A promising Diagnostic Biomarker in Experimental Toxoplasmosis Using Different Strains and Infective Doses in Mice with Different Immune States Before and After Treatment

IF 1.2 3区农林科学 Q4 PARASITOLOGY Acta Parasitologica Pub Date : 2024-05-14 DOI:10.1007/s11686-024-00851-w

Rasha Fadly Mady, Mona Mohamed El-Temsahy, Yasmine Amr Issa, Aya Saied Zaghloul, Safaa Ibrahim Khedr

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Abstract

Purpose

Searching for a novel early diagnostic biomarker for toxoplasmosis, real-time-PCR was currently used to measure the serum mmu-miR-511-5p level in male Swiss-albino mice infected with either; ME49 or RH Toxoplasma gondii (T. gondii) strains.

Methods

Three mice groups were used; (GI) constituted the non-infected control group, while (GII) and (GIII) were experimentally infected with ME49 or RH strains, respectively. GII mice were orally infected using 10 or 20 ME49 cysts (ME-10 and ME-20), both were subdivided into; non-treated (ME-10-NT and ME-20-NT) and were further subdivided into; immunocompetent (ME-10-IC and ME-20-IC) [euthanized 3-days, 1, 2, 6 or 8-weeks post-infection (PI)], and immunosuppressed using two Endoxan^® injections (ME-10-IS and ME-20-IS) [euthanized 6- or 8-weeks PI], and spiramycin-treated (ME-10-SP and ME-20-SP) that received daily spiramycin, for one-week before euthanasia. GIII mice individually received 2500 intraperitoneal RH strain tachyzoites, then, were subdivided into; non-treated (RH-NT) [euthanized 3 or 5-days PI], and spiramycin-treated (RH-SP) that were euthanized 5 or 10-days PI (refer to the graphical abstract).

Results

Revealed significant upregulation of mmu-miR-511-5p in GII, one-week PI, with gradually increased expression, reaching its maximum 8-weeks PI, especially in ME-20-NT group that received the higher infective dose. Immunosuppression increased the upregulation. Contrarily, treatment caused significant downregulation. GIII recorded significant upregulation 3-days PI, yet, treatment significantly decreased this expression.

Conclusion

Serum mmu-miR-511-5p is a sensitive biomarker for early diagnosis of ME49 and RH infection (as early as one-week and 3-days, respectively), and its expression varies according to T. gondii infective dose, duration of infection, spiramycin-treatment and host immune status.

Graphical abstract

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微RNA mmu-miR-511-5p：使用不同菌株和感染剂量对治疗前后免疫状态不同的小鼠进行实验性弓形虫病诊断的有望生物标记物

目的：为了寻找一种新型的弓形虫病早期诊断生物标志物，目前采用实时荧光定量PCR技术测量感染了ME49或RH弓形虫（T. gondii）菌株的雄性瑞士阿尔比诺小鼠的血清mmu-miR-511-5p水平：方法：使用三组小鼠：(GI) 为未感染对照组，(GII) 和 (GIII) 分别实验感染 ME49 或 RH 毒株。GII 小鼠口服感染了 10 个或 20 个 ME49 囊肿（ME-10 和 ME-20），两者又被细分为：未处理组（ME-10-NT 和 ME-20-NT），并进一步细分为免疫功能正常（ME-10-IC 和 ME-20-IC）[感染后 3 天、1、2、6 或 8 周（PI）安乐死]；注射两次 Endoxan® 的免疫抑制（ME-10-IS 和 ME-20-IS）[感染后 6 或 8 周（PI）安乐死]；接受螺旋霉素治疗（ME-10-SP 和 ME-20-SP）的小鼠在安乐死前一周每天接受螺旋霉素治疗。GIII 小鼠分别腹腔注射了 2500 头 RH 株小鼠，然后被细分为：未经处理（RH-NT）[安乐死前 3 天或 5 天]，以及螺旋霉素处理（RH-SP），安乐死前 5 天或 10 天（参见图表摘要）：结果表明：GII中mmu-miR-511-5p的表达在一周PI时明显上调，并逐渐增加，在8周PI时达到最大值，尤其是在接受较高感染剂量的ME-20-NT组。免疫抑制增加了上调。相反，治疗则会导致明显的下调。GIII 组在感染前 3 天出现了明显的上调，但治疗会显著降低这种表达：血清mmu-miR-511-5p是早期诊断ME49和RH感染（分别早至一周和3天）的敏感生物标志物，其表达随淋球菌感染剂量、感染持续时间、螺旋霉素治疗和宿主免疫状态而变化。

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来源期刊

Acta Parasitologica 医学-寄生虫学

CiteScore

3.10

自引率

6.70%

发文量

149

审稿时长

6-12 weeks

期刊介绍： Acta Parasitologica is an international journal covering the latest advances in the subject. Acta Parasitologica publishes original papers on all aspects of parasitology and host-parasite relationships, including the latest discoveries in biochemical and molecular biology of parasites, their physiology, morphology, taxonomy and ecology, as well as original research papers on immunology, pathology, and epidemiology of parasitic diseases in the context of medical, veterinary and biological sciences. The journal also publishes short research notes, invited review articles, book reviews. The journal was founded in 1953 as "Acta Parasitologica Polonica" by the Polish Parasitological Society and since 1954 has been published by W. Stefanski Institute of Parasitology of the Polish Academy of Sciences in Warsaw. Since 1992 in has appeared as Acta Parasitologica in four issues per year.