Argueta-Donohué Jesús, Carrillo Nuria, Valdés-Reyes Leonardo, Zentella Alejandro, Aguirre-García Magdalena, Becker Ingeborg, Gutiérrez-Kobeh Laila
Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis 148, Col. Doctores, México 06726, Mexico.
Exp Parasitol. 2008 Sep;120(1):1-9. doi: 10.1016/j.exppara.2008.04.002. Epub 2008 Apr 11.
Dendritic cells (DC) and macrophages (Mphi) are well known as important effectors of the innate immune system and their ability to produce IL-12 indicates that they possess the potential of directing acquired immunity toward a Th1-biased response. Interestingly, the intracellular parasite Leishmania has been shown to selectively suppress Mphi IL-12 production and are DC the principal source of this cytokine. The molecular details of this phenomenon remain enigmatic. In the present study we examined the effect of Leishmania mexicana lipophosphoglycan (LPG) on the production of IL-12, TNF-alpha, and IL-10 and nuclear translocation of NF-kappaB. The results show that LPG induced more IL-12 in human DC than in monocytes. This difference was due in part to nuclear translocation of NF-kappaB, since LPG induced more translocation in DC than in monocytes. These results suggest that Leishmania LPG impairs nuclear translocation of NF-kappaB in monocytes with the subsequent decrease in IL-12 production.
树突状细胞（DC）和巨噬细胞（Mphi）作为天然免疫系统的重要效应器广为人知，它们产生白细胞介素-12（IL-12）的能力表明它们具有引导获得性免疫向Th1偏向性反应发展的潜力。有趣的是，细胞内寄生虫利什曼原虫已被证明能选择性抑制Mphi产生IL-12，而DC是这种细胞因子的主要来源。这一现象的分子细节仍然不明。在本研究中，我们检测了墨西哥利什曼原虫脂磷壁酸（LPG）对IL-12、肿瘤坏死因子-α（TNF-α）和IL-10产生以及核因子-κB（NF-κB）核转位的影响。结果显示，LPG在人DC中诱导产生的IL-12比在单核细胞中更多。这种差异部分归因于NF-κB的核转位，因为LPG在DC中诱导的核转位比在单核细胞中更多。这些结果表明，利什曼原虫LPG损害单核细胞中NF-κB的核转位，随后导致IL-12产生减少。
