Contreras Irazú, Estrada José A, Guak Hannah, Martel Caroline, Borjian Alborz, Ralph Benjamin, Shio Marina T, Fournier Sylvie, Krawczyk Connie M, Olivier Martin
Department of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada; Neurochemistry Laboratory, Faculty of Medicine. Universidad Autónoma del Estado de México, Toluca, Estado de México, México.
Department of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada.
PLoS Negl Trop Dis. 2014 Sep 25;8(9):e3202. doi: 10.1371/journal.pntd.0003202. eCollection 2014 Sep.
Leishmania parasites have the ability to modify macrophage signaling pathways in order to survive and multiply within its mammalian host. They are also known to invade other cells including neutrophils, fibroblasts and dendritic cells (DCs). DCs have an important role in immunity as the link between innate and adaptive immunity, necessary for the development of an effective response; however, the impact of Leishmania mexicana infection on DCs has been poorly studied. Herein, we report that Leishmania infection rapidly induced DC protein tyrosine phosphatases activity, leading to MAP kinases inactivation. In line with this, L. mexicana was found to decrease the nuclear translocation of transcription factors such as AP-1 and NF-κB. Concomitantly, L. mexicana-infected DCs showed reduced expression of several surface antigen-presenting and co-stimulatory molecules upon LPS stimulation. Leishmania-induced interference on DC maturation was further reflected by their reduced capacity to present OVA antigen to OVA-specific T cells, as shown by abrogation of IL-2 production by the T cells. Collectively, our data revealed that DC infection by L. mexicana appears to affect the cellular and immunological mechanisms necessary for the development of an effective and protective immune response, therefore favouring the survival and propagation of the parasite within its host.
利什曼原虫具有改变巨噬细胞信号通路的能力,以便在其哺乳动物宿主内存活和繁殖。它们还已知会侵入包括中性粒细胞、成纤维细胞和树突状细胞(DCs)在内的其他细胞。DCs作为先天性免疫和适应性免疫之间的联系,在免疫中起着重要作用,是有效免疫反应发展所必需的;然而,墨西哥利什曼原虫感染对DCs的影响研究甚少。在此,我们报告利什曼原虫感染迅速诱导DC蛋白酪氨酸磷酸酶活性,导致丝裂原活化蛋白激酶失活。与此一致的是,发现墨西哥利什曼原虫会减少转录因子如AP-1和NF-κB的核转位。同时,经脂多糖刺激后,感染墨西哥利什曼原虫的DCs显示出几种表面抗原呈递分子和共刺激分子的表达降低。利什曼原虫诱导的对DC成熟的干扰进一步体现在它们向OVA特异性T细胞呈递OVA抗原的能力降低,如T细胞产生IL-2的能力被消除所示。总体而言,我们的数据表明,墨西哥利什曼原虫感染DCs似乎会影响有效和保护性免疫反应发展所需的细胞和免疫机制,从而有利于寄生虫在其宿主体内的存活和繁殖。