Abstract
Dendritic cells (DCs) are one of the principal host cells of the obligate intracellular parasite Leishmania that can survive and reproduce within cells due to the ability to regulate different cellular events, including apoptosis. Inhibition of host cell apoptosis is a strategy employed by multiple pathogens to ensure their survival in the infected cell. We have previously reported that Leishmania mexicana promastigotes and amastigotes inhibit camptothecin-induced apoptosis of monocyte-derived dendritic cells (moDCs) through the downregulation of p38 and JNK phosphorylation. The upregulation of glutathione (GSH), the most important regulator of reactive oxygen species (ROS) concentration, has proven to protect cells from apoptosis through the inhibition of JNK1. Another mechanism employed by cells for the protection of apoptosis is the expression of anti-apoptotic proteins of the Bcl-2 family. The aim of this study was to determine if GSH, ROS, and Bcl-xL participate in the inhibition of camptothecin-induced apoptosis of moDC by L. mexicana promastigotes. GSH quantification assays showed that camptothecin and BSO (an inhibitor of glutathione synthesis) strongly decreased intracellular GSH concentration in moDC, while infection with L. mexicana promastigotes had no effect in the level of GSH. On the other hand, infection with L. mexicana promastigotes of BSO- and camptothecin-treated moDC diminished the concentration of ROS and induced the expression of the anti-apoptotic protein Bcl-xL. Our findings suggest that inhibition of camptothecin-induced apoptosis of moDC by L. mexicana promastigotes is preferentially regulated by the expression of anti-apoptotic proteins of the Bcl-2 family rather than by the redox status of the cell.
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Acknowledgements
We thank Dr. Alfonso Olivos García for his valuable help with the ROS determinations.
This work was supported by grant IN225116 from Papiit, DGAPA-UNAM. Jorge Rodríguez-González is a Ph. D student of Posgrado en Ciencias Biológicas, Facultad de Medicina, Universidad Nacional Autónoma de México and is recipient of a CONACyT fellowship, number 481304.
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Informed consent was obtained for the use of blood samples according to the Declaration of Helsinki and the Comisiones de Investigación y Ética de la Facultad de Medicina, Universidad Nacional Autónoma de México approved the protocol with number 104/2015 on August 25, 2015 with a validity of 3 years.
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Rodríguez-González, J., Wilkins-Rodríguez, A.A. & Gutiérrez-Kobeh, L. Role of glutathione, ROS, and Bcl-xL in the inhibition of apoptosis of monocyte-derived dendritic cells by Leishmania mexicana promastigotes. Parasitol Res 117, 1225–1235 (2018). https://doi.org/10.1007/s00436-018-5804-z
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DOI: https://doi.org/10.1007/s00436-018-5804-z