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咪喹莫特通过调节宿主 Toll 样受体-髓样分化因子 88 信号通路靶向弓形虫病。

Imiquimod Targets Toxoplasmosis Through Modulating Host Toll-Like Receptor-MyD88 Signaling.

机构信息

Department of Experimental Pathology, Microbiology and Immunology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

IBMM, Université de Montpellier, CNRS, ENSCM, Montpellier, France.

出版信息

Front Immunol. 2021 Mar 9;12:629917. doi: 10.3389/fimmu.2021.629917. eCollection 2021.

Abstract

is a prevalent parasite of medical and veterinary importance. Tachyzoïtes and bradyzoïtes are responsible for acute and chronic toxoplasmosis (AT and CT), respectively. In immunocompetent hosts, AT evolves into a persistent CT, which can reactivate in immunocompromised patients with dire consequences. Imiquimod is an efficient immunomodulatory drug against certain viral and parasitic infections. , treatment with Imiquimod, throughout AT, reduces the number of brain cysts while rendering the remaining cysts un-infectious. Post-establishment of CT, Imiquimod significantly reduces the number of brain cysts, leading to a delay or abortion of reactivation. At the molecular level, Imiquimod upregulates the expression of Toll-like receptors 7, 11, and 12, following interconversion from bradyzoïtes to tachyzoïtes. Consequently, MyD88 pathway is activated, resulting in the induction of the immune response to control reactivated foci. This study positions Imiquimod as a potent drug against toxoplasmosis and elucidates its mechanism of action particularly against chronic toxoplasmosis, which is the most prevalent form of the disease.

摘要

刚地弓形虫是一种具有医学和兽医重要性的流行寄生虫。速殖子和缓殖子分别导致急性和慢性弓形虫病(AT 和 CT)。在免疫功能正常的宿主中,AT 演变为持续的 CT,在免疫功能低下的患者中可能重新激活,导致严重后果。咪喹莫特是一种有效的免疫调节药物,可用于治疗某些病毒和寄生虫感染。在 AT 期间,咪喹莫特治疗可减少脑囊虫数量,使剩余的囊虫失去感染力。在 CT 建立后,咪喹莫特可显著减少脑囊虫数量,从而延迟或阻止其重新激活。在分子水平上,咪喹莫特在从缓殖子转化为速殖子时上调 Toll 样受体 7、11 和 12 的表达。随后,MyD88 通路被激活,导致诱导免疫反应以控制重新激活的病灶。这项研究将咪喹莫特定位为一种对抗弓形虫病的有效药物,并阐明了其对慢性弓形虫病(最常见的疾病形式)的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2237/7986122/4b51d456fbc6/fimmu-12-629917-g0001.jpg

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