Margaroni Maritsa, Agallou Maria, Vasilakaki Athina, Karagkouni Dimitra, Skoufos Giorgos, Hatzigeorgiou Artemis G, Karagouni Evdokia
Immunology of Infection Laboratory, Department of Microbiology, Hellenic Pasteur Institute, 11521 Athens, Greece.
DIANA-Lab, Department of Computer Science and Biomedical Informatics, University of Thessaly, 35131 Lamia, Greece.
Microorganisms. 2022 Jun 22;10(7):1271. doi: 10.3390/microorganisms10071271.
parasites are capable of effectively invading dendritic cells (DCs), a cell population orchestrating immune responses against several diseases, including leishmaniasis, by bridging innate and adaptive immunity. on the other hand has evolved various mechanisms to subvert DCs activation and establish infection. Thus, the transcriptional profile of DCs derived from bone marrow (BMDCs) that have been infected with parasite or of DCs exposed to chemically inactivated parasites was investigated via RNA sequencing, aiming to better understand the host-pathogen interplay. Flow cytometry analysis revealed that actively inhibits maturation of not only infected but also bystander BMDCs. Analysis of double-sorted infected BMDCs revealed significantly increased expression of genes mainly associated with metabolism and particularly glycolysis. Moreover, differentially expressed genes (DEGs) related to DC-T cell interactions were also found to be upregulated exclusively in infected BMDCs. On the contrary, transcriptome analysis of fixed parasites containing BMDCs indicated that energy production was mediated through TCA cycle and oxidative phosphorylation. In addition, DEGs related to differentiation of DCs leading to activation and differentiation of Th17 subpopulations were detected. These findings suggest an important role of metabolism on DCs- interplay and eventually disease establishment.
寄生虫能够有效侵入树突状细胞（DCs），树突状细胞群体通过连接固有免疫和适应性免疫来协调针对包括利什曼病在内的多种疾病的免疫反应。另一方面，寄生虫进化出了各种机制来破坏树突状细胞的激活并建立感染。因此，通过RNA测序研究了感染寄生虫的骨髓来源树突状细胞（BMDCs）或暴露于化学灭活寄生虫的树突状细胞的转录谱，旨在更好地理解宿主 - 病原体相互作用。流式细胞术分析表明，寄生虫不仅能抑制受感染的BMDCs成熟，还能抑制旁观者BMDCs的成熟。对双重分选的感染BMDCs的分析显示，主要与代谢特别是糖酵解相关的基因表达显著增加。此外，还发现与DC - T细胞相互作用相关的差异表达基因（DEGs）仅在受感染的BMDCs中上调。相反，对含有固定寄生虫的BMDCs的转录组分析表明，能量产生是通过三羧酸循环和氧化磷酸化介导的。此外，还检测到与树突状细胞分化相关的DEGs，这些分化导致Th17亚群的激活和分化。这些发现表明代谢在树突状细胞相互作用以及最终疾病发生中起着重要作用。
