Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
Department of Immunology, School of Medicine, Universidad Autonoma de San Luis Potosi, San Luis Potosi, Mexico.
Pathog Dis. 2018 Mar 1;76(2). doi: 10.1093/femspd/fty005.
Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb). Innate immunity is the first line of defense against Mtb and malfunctions in any of its components are associated with the susceptibility to the disease. Epithelial products such as host defense peptides (HDPs) are the first molecules produced to counteract the infection. Although a wide variety of HDPs are produced by epithelial cells only a few of them have been studied during Mtb infection. Here, we assessed the expression and production of the HDPs psoriasin, secreted phospholipases A2 (sPLA2-IIA) and Ribonuclease (RNase) 7 in airway epithelial cells (NCI-H292), type II pneumocytes (A549 cells) and monocyte-derived macrophages from human peripheral blood mononuclear cells and from the human cell line THP1 after Mtb in vitro infection. Results show that psoriasin and sPLA2-IIA were not induced by Mtb in any of the evaluated cells, while RNase 7 was overexpressed in infected airway epithelial cells. Intracellular analysis by flow cytometry demonstrated that the highest levels of RNase 7 were observed 6 h post-infection and the induction was dependent on direct interaction between airway epithelial cells and Mtb. In addition, analysis by electron microscopy showed that RNase 7 was capable of attaching to the cell wall of intracellular mycobacteria. Our studies suggest that the induction of RNase 7 in response to Mtb could have a role in anti-mycobacterial immunity, which needs to be studied as an innate immune mechanism.
结核病是由结核分枝杆菌(Mtb)引起的疾病。固有免疫是抵御 Mtb 的第一道防线,其任何成分的功能障碍都与对该疾病的易感性有关。上皮细胞产物,如宿主防御肽(HDPs),是产生的第一批对抗感染的分子。尽管上皮细胞产生了多种 HDPs,但在 Mtb 感染期间仅对其中少数进行了研究。在这里,我们评估了气道上皮细胞(NCI-H292)、II 型肺细胞(A549 细胞)和人外周血单核细胞来源的单核细胞衍生巨噬细胞以及人细胞系 THP1 中 HDP 角鲨胺、分泌型磷脂酶 A2(sPLA2-IIA)和核糖核酸酶 7 的表达和产生在 Mtb 体外感染后。结果表明,在评估的任何细胞中,Mtb 均未诱导角鲨胺和 sPLA2-IIA,而 RNase 7 在感染的气道上皮细胞中过度表达。通过流式细胞术进行的细胞内分析表明,RNase 7 的最高水平在感染后 6 小时观察到,诱导依赖于气道上皮细胞与 Mtb 的直接相互作用。此外,电子显微镜分析表明,RNase 7 能够附着在细胞内分枝杆菌的细胞壁上。我们的研究表明,针对 Mtb 诱导的 RNase 7 的诱导可能在抗分枝杆菌免疫中起作用,这需要作为一种先天免疫机制进行研究。