Potential i-Nos/Arg-1 Switch with NLRP3 and Parasitic Load Down Regulation in Experimental Schistosoma mansoni Infection via Chloroquine Repurposing.

IF 1.4 4区 医学 Q4 IMMUNOLOGY
Marwa A Hasby Saad, Esraa G El-Saadi, Dareen A Ali, Mona M Watany, Mohammed M Eid
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引用次数: 0

Abstract

In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double-bladed sword in schistosomiasis (anti-inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i-Nos/Arg-1 expression, splenomegaly, hepatic insult and NLRP3-immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel-induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i-Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i-Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage-1 polarisation. On the flip side, the chloroquine-induced low Arg-1 seemed to abate immune tolerance and probably macrophage-2 polarisation. Collectively, chloroquine synergised the praziquantel-schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis.

通过氯喹再利用,在实验性曼氏血吸虫感染中潜在的 i-Nos/Arg-1 开关与 NLRP3 和寄生虫负荷下调作用
以往的研究表明,氯喹对 NLRP3 炎症小体和血红素的产生有抑制作用。这可能是血吸虫病的一把双刃剑(抗炎和杀寄生虫)。本研究调查了氯喹对曼氏血吸虫病的影响。研究人员评估了感染小鼠在单独或与吡喹酮同时接受早期和晚期重复剂量氯喹治疗后的寄生虫量(虫/卵计数和生殖能力指数[RCI])、i-Nos/Arg-1表达、脾肿大、肝损伤和NLRP3免疫组化表达。与单用氯喹或吡喹酮相比,早期治疗的小鼠RCI最低(41.48 ± 28.58),虫卵数显著减少(3.50 ± 1.29/2550 ± 479.58)。长期服用氯喹可显著降低脾脏指数(单用:43.15 ± 5.67,双用:36.03 ± 5.27),其纤维化程度(15 ± 3.37,14.25 ± 2.22)明显低于单用吡喹酮(20.5 ± 2.65)。在炎症方面,尽管吡喹酮诱导的 NLRP3 表达显著下降,但双联和氯喹给药后抑制作用明显(肝脏:3.13 ± 1.21/3.i-Nos RNA 在氯喹给药早期/晚期达到峰值(肝脏:68.53 ± 1.8/57.78 ± 7.14,脾脏:63.22 ± 2.06/62.5 ± 3.05)。高 i-Nos 与杀寄生虫和保肝作用相呼应,可能表明巨噬细胞-1 极化。另一方面,氯喹诱导的低 Arg-1 似乎会降低免疫耐受性,并可能导致巨噬细胞-2 极化。总之,氯喹可协同吡喹酮-杀螺囊虫作用,最大程度地减轻组织炎症、脾肿大和肝纤维化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Parasite Immunology
Parasite Immunology 医学-寄生虫学
CiteScore
4.70
自引率
4.50%
发文量
61
审稿时长
6-12 weeks
期刊介绍: Parasite Immunology is an international journal devoted to research on all aspects of parasite immunology in human and animal hosts. Emphasis has been placed on how hosts control parasites, and the immunopathological reactions which take place in the course of parasitic infections. The Journal welcomes original work on all parasites, particularly human parasitology, helminths, protozoa and ectoparasites.
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