墨西哥利什曼原虫:对喜树碱诱导的单核细胞衍生树突状细胞凋亡的抑制作用

Leishmania mexicana: inhibition of camptothecin-induced apoptosis of monocyte-derived dendritic cells.

作者信息

Valdés-Reyes Leonardo, Argueta Jesús, Morán Julio, Salaiza Norma, Hernández Joselín, Berzunza Miriam, Aguirre-García Magdalena, Becker Ingeborg, Gutiérrez-Kobeh Laila

机构信息

Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis 148, Col. Doctores, México, D.F. 06726, Mexico.

出版信息

Exp Parasitol. 2009 Mar;121(3):199-207. doi: 10.1016/j.exppara.2008.10.020. Epub 2008 Nov 18.

Abstract

Macrophages (Mphi) and dendritic cells (DC) are the major target cell populations of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a method employed by multiple pathogens to ensure their survival in the infected cell. Leishmania has been shown to protect Mphi and neutrophils from both natural and induced apoptosis. As shown in this study, apoptosis in monocyte-derived dendritic cells (moDC) induced by treatment with camptothecin was downregulated by coincubation with L. mexicana, as detected by morphological analysis of cell nuclei, TUNEL assay, gel electrophoresis of low molecular weight DNA fragments, and annexin V binding to phosphatidylserine. The observed antiapoptotic effect was found to be associated with a significant reduction of caspase-3 activity in moDC. The capacity of L. mexicana to delay apoptosis induction in the infected moDC may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.

摘要

巨噬细胞(Mphi)和树突状细胞(DC)是专性细胞内寄生虫利什曼原虫的主要靶细胞群体。抑制宿主细胞凋亡是多种病原体用来确保其在感染细胞中存活的一种方法。利什曼原虫已被证明可保护巨噬细胞和中性粒细胞免受自然凋亡和诱导凋亡。如本研究所示,通过细胞核形态分析、TUNEL检测、低分子量DNA片段凝胶电泳以及膜联蛋白V与磷脂酰丝氨酸结合检测发现,与墨西哥利什曼原虫共同孵育可下调喜树碱处理诱导的单核细胞衍生树突状细胞(moDC)凋亡。观察到的抗凋亡作用与moDC中半胱天冬酶-3活性的显著降低有关。墨西哥利什曼原虫延迟感染的moDC凋亡诱导的能力可能通过促进其宿主的侵袭和寄生虫在感染细胞中的持续存在而对利什曼原虫的发病机制产生影响。

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