Department of Immunology. Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
Department of Immunology, ENCB-IPN, Mexico City, Mexico.
J Leukoc Biol. 2018 Apr;103(4):731-738. doi: 10.1002/JLB.4AB0517-184R. Epub 2017 Dec 27.
In this work, we identified the expression, regulation, and viral targeting of Scribble and Dlg1 in antigen-presenting cells. Scribble and Dlg1 belong to the family of PDZ (postsynaptic density (PSD95), disc large (Dlg), and zonula occludens (ZO-1)) proteins involved in cell polarity. The relevance of PDZ proteins in cellular functions is reinforced by the fact that many viruses interfere with host PDZ-dependent interactions affecting cellular mechanisms thus favoring viral replication. The functions of Scribble and Dlg have been widely studied in polarized cells such as epithelial and neuron cells. However, within the cells of the immune system, their functions have been described only in T and B lymphocytes. Here we demonstrated that Scribble and Dlg1 are differentially expressed during antigen-presenting cell differentiation and dendritic cell maturation. While both Scribble and Dlg1 seem to participate in distinct dendritic cell functions, both are targeted by the viral protein NS1 of influenza A in a PDZ-dependent manner in dendritic cells. Our findings suggest that these proteins might be involved in the mechanisms of innate immunity and/or antigen processing and presentation that can be hijacked by viral pathogens.
在这项工作中,我们确定了 Scribble 和 Dlg1 在抗原呈递细胞中的表达、调控和病毒靶向。Scribble 和 Dlg1 属于 PDZ(突触后密度(PSD95)、Disc large(Dlg)和封闭带(ZO-1))蛋白家族,参与细胞极性。PDZ 蛋白在细胞功能中的相关性得到了加强,因为许多病毒会干扰宿主 PDZ 依赖性相互作用,从而影响细胞机制,从而有利于病毒复制。Scribble 和 Dlg 的功能已在极化细胞(如上皮细胞和神经元细胞)中得到广泛研究。然而,在免疫系统的细胞中,它们的功能仅在 T 和 B 淋巴细胞中得到描述。在这里,我们证明 Scribble 和 Dlg1 在抗原呈递细胞分化和树突状细胞成熟过程中差异表达。虽然 Scribble 和 Dlg1 似乎都参与了树突状细胞的不同功能,但两者都被流感 A 病毒的 NS1 蛋白以 PDZ 依赖性的方式靶向,在树突状细胞中。我们的发现表明,这些蛋白可能参与先天免疫和/或抗原加工和呈递的机制,这些机制可能被病毒病原体劫持。