Fernández-Figueroa Edith A, Imaz-Rosshandler Iván, Castillo-Fernández Juan E, Miranda-Ortíz Haydee, Fernández-López Juan C, Becker Ingeborg, Rangel-Escareño Claudia
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, C.P.04510 México, D.F., México.
Unidad de Investigación en Medicina Experimental, Centro de Medicina Tropical, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida, D.F., México.
PLoS Negl Trop Dis. 2016 Mar 31;10(3):e0004570. doi: 10.1371/journal.pntd.0004570. eCollection 2016 Mar.
An important NK-cell inhibition with reduced TNF-α, IFN-γ and TLR2 expression had previously been identified in patients with diffuse cutaneous leishmaniasis (DCL) infected with Leishmania mexicana. In an attempt to pinpoint alterations in the signaling pathways responsible for the NK-cell dysfunction in patients with DCL, this study aimed at identifying differences in the NK-cell response towards Leishmania mexicana lipophosphoglycan (LPG) between patients with localized and diffuse cutaneous leishmaniasis through gene expression profiling. Our results indicate that important genes involved in the innate immune response to Leishmania are down-regulated in NK cells from DCL patients, particularly TLR and JAK/STAT signaling pathways. This down-regulation showed to be independent of LPG stimulation. The study sheds new light for understanding the mechanisms that undermine the correct effector functions of NK cells in patients with diffuse cutaneous leishmaniasis contributing to a better understanding of the pathobiology of leishmaniasis.
先前已在感染墨西哥利什曼原虫的弥漫性皮肤利什曼病（DCL）患者中发现了一种重要的自然杀伤（NK）细胞抑制现象，其肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和Toll样受体2（TLR2）表达降低。为了确定导致DCL患者NK细胞功能障碍的信号通路改变，本研究旨在通过基因表达谱分析，找出局部性和弥漫性皮肤利什曼病患者的NK细胞对墨西哥利什曼原虫脂磷壁酸聚糖（LPG）反应的差异。我们的结果表明，参与对利什曼原虫固有免疫反应的重要基因在DCL患者的NK细胞中表达下调，特别是TLR和JAK/STAT信号通路。这种下调显示与LPG刺激无关。该研究为理解破坏弥漫性皮肤利什曼病患者NK细胞正确效应功能的机制提供了新线索，有助于更好地理解利什曼病的病理生物学。
