墨西哥利什曼原虫无鞭毛体抑制p38和JNK并激活PI3K/AKT:在抑制树突状细胞凋亡中的作用

Leishmania mexicana amastigotes inhibit p38 and JNK and activate PI3K/AKT: role in the inhibition of apoptosis of dendritic cells.

作者信息

Vázquez-López R, Argueta-Donohué J, Wilkins-Rodríguez A, Escalona-Montaño A, Aguirre-García M, Gutiérrez-Kobeh L

机构信息

Laboratorio de Microbiología y Parasitología, Facultad de Ciencias de la Salud, Av. Universidad Anáhuac Norte, Lomas Anáhuac, Huixquilucan, México.

Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. México.

出版信息

Parasite Immunol. 2015 Nov;37(11):579-89. doi: 10.1111/pim.12275.

Abstract

Leishmania mexicana is the causal agent of cutaneous leishmaniasis in Mexico. Dendritic cells (DC) are one of the host cells of Leishmania parasites. Intracellular microorganisms inhibit host cell apoptosis as a strategy to ensure their survival in infected cells. We have previously shown that Leishmania mexicana promastigotes and amastigotes inhibit camptothecin-induced apoptosis of monocyte-derived dendritic cells (moDC), but the mechanisms underlying the inhibition of apoptosis of DC by Leishmania have not been established. MAP kinases and PI3K participate in the process of apoptosis and are modulated by different species of Leishmania. As shown in this study, the infection of moDC with L. mexicana amastigotes diminished significantly the phosphorylation of the MAP kinases p38 and JNK. The inhibition of both kinases diminished significantly DNA fragmentation in moDC stimulated with camptothecin. On the other hand, L. mexicana amastigotes were able to activate the anti-apoptotic pathways PI3K and AKT. Our results indicate that L. mexicana amastigotes have the capacity to diminish MAP kinases activation and activate PI3K and AKT, which is probably one of the strategies employed by L. mexicana amastigotes to inhibit apoptosis in the infected moDC.

摘要

墨西哥利什曼原虫是墨西哥皮肤利什曼病的病原体。树突状细胞(DC)是利什曼原虫的宿主细胞之一。细胞内微生物抑制宿主细胞凋亡,以此作为确保其在感染细胞中存活的一种策略。我们之前已经表明,墨西哥利什曼原虫前鞭毛体和无鞭毛体可抑制喜树碱诱导的单核细胞衍生树突状细胞(moDC)凋亡,但利什曼原虫抑制DC凋亡的潜在机制尚未明确。丝裂原活化蛋白激酶(MAP激酶)和磷脂酰肌醇-3激酶(PI3K)参与凋亡过程,并受到不同种类利什曼原虫的调控。如本研究所示,墨西哥利什曼原虫无鞭毛体感染moDC可显著降低MAP激酶p38和JNK的磷酸化水平。对这两种激酶的抑制可显著减少喜树碱刺激的moDC中的DNA片段化。另一方面,墨西哥利什曼原虫无鞭毛体能够激活抗凋亡途径PI3K和蛋白激酶B(AKT)。我们的结果表明,墨西哥利什曼原虫无鞭毛体有能力减少MAP激酶的激活并激活PI3K和AKT,这可能是墨西哥利什曼原虫无鞭毛体抑制感染的moDC凋亡所采用的策略之一。

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