Villaseñor Tomás, Madrid-Paulino Edgardo, Maldonado-Bravo Rafael, Urbán-Aragón Antonio, Pérez-Martínez Leonor, Pedraza-Alva Gustavo
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México , Cuernavaca, Morelos , Mexico.
Front Immunol. 2017 Feb 1;8:50. doi: 10.3389/fimmu.2017.00050. eCollection 2017.
(), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against . The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN. interaction with any of these receptors activates multiple signaling pathways among which the protein kinase C, the MAPK, and the NFκB pathways have been widely studied. These pathways have been implicated in macrophage invasion, survival, and impaired immune response, thus promoting a successful infection and disease. Interestingly, the Wnt signaling pathway, classically regarded as a pathway involved in the control of cell proliferation, migration, and differentiation in embryonic development, has recently been involved in immunoregulatory mechanisms in infectious and inflammatory diseases, such as TB, sepsis, psoriasis, rheumatoid arthritis, and atherosclerosis. In this review, we present the current knowledge supporting a role for the Wnt signaling pathway during macrophage infection by and the regulation of the immune response against . Understanding the cross talk between different signaling pathways activated by will impact on the search for new therapeutic targets to fuel the rational design of drugs aimed to restore the immunological response against .
结核分枝杆菌，一种细胞内致病性革兰氏阳性细菌，是结核病（TB）的病原体，结核病是一种全球范围内主要的人类传染病。固有免疫系统是宿主抵御结核分枝杆菌的第一道防线。对这种病原体的识别由宿主固有免疫细胞上表达的几类模式识别受体介导，包括Toll样受体、Nod样受体以及C型凝集素受体，如树突状细胞相关C型凝集素-1、甘露糖受体和树突状细胞特异性细胞间黏附分子-3抓取非整合素。结核分枝杆菌与这些受体中的任何一种相互作用都会激活多种信号通路，其中蛋白激酶C、丝裂原活化蛋白激酶和核因子κB通路已得到广泛研究。这些通路与巨噬细胞侵袭、结核分枝杆菌存活以及免疫反应受损有关，从而促进感染和疾病的发生。有趣的是，经典的Wnt信号通路被认为是参与胚胎发育中细胞增殖、迁移和分化控制的通路，最近它也参与了感染性和炎症性疾病（如结核病、败血症、银屑病、类风湿性关节炎和动脉粥样硬化）的免疫调节机制。在这篇综述中，我们介绍了目前支持Wnt信号通路在巨噬细胞感染结核分枝杆菌期间发挥作用以及调节针对结核分枝杆菌免疫反应的相关知识。了解结核分枝杆菌激活的不同信号通路之间的相互作用，将有助于寻找新的治疗靶点，从而推动旨在恢复针对结核分枝杆菌免疫反应的药物的合理设计。
