Mortaz Esmaeil, Adcock Ian M, Abedini Atefhe, Kiani Arda, Kazempour-Dizaji Mehdi, Movassaghi Masoud, Garssen Johan
Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
Eur J Pharmacol. 2017 Aug 5;808:44-48. doi: 10.1016/j.ejphar.2017.01.020. Epub 2017 Jan 17.
Sarcoidosis is a granulomatous disorder of unknown etiology. Infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. The etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. Inflammation results from recognition of evolutionarily conserved structures of pathogens (Pathogen-associated molecular patterns, PAMPs) and/or from reaction to tissue damage associated patterns (DAMPs) through recognition by a limited number of germ line-encoded pattern recognition receptors (PRRs). Due to the similar clinical and histopathological picture of sarcoidosis and tuberculosis, Mycobacterium tuberculosis antigens such early secreted antigen (ESAT-6), heat shock proteins (Mtb-HSP), catalase-peroxidase (katG) enzyme and superoxide dismutase A peptide (sodA) have been often considered as factors in the etiopathogenesis of sarcoidosis. Potential non-TB-associated PAMPs include lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria, peptidoglycan, lipoteichoic acid, bacterial DNA, viral DNA/RNA, chitin, flagellin, leucine-rich repeats (LRR), mannans in the yeast cell wall, and microbial HSPs. Furthermore, exogenous non-organic antigens such as metals, silica, pigments with/without aluminum in tattoos, pesticides, and pollen have been evoked as potential causes of sarcoidosis. Exposure of the airways to diverse infectious and non-infectious agents may be important in the pathogenesis of sarcoidosis. The current review provides and update on the role of PPRs and DAMPs in the pathogenesis of sarcoidsis.
结节病是一种病因不明的肉芽肿性疾病。感染、遗传因素、自身免疫和异常的固有免疫系统已被探讨为结节病的潜在病因。结节病的病因仍然不明，人们认为它可能是由遗传易感性、易感宿主中的感染因子引起的。炎症是由于识别病原体进化上保守的结构（病原体相关分子模式，PAMPs）和/或通过有限数量的种系编码模式识别受体（PRRs）识别与组织损伤相关的模式（DAMPs）而产生的。由于结节病和结核病在临床和组织病理学表现上相似，结核分枝杆菌抗原如早期分泌抗原（ESAT-6）、热休克蛋白（Mtb-HSP）、过氧化氢酶-过氧化物酶（katG）酶和超氧化物歧化酶A肽（sodA）常被认为是结节病发病机制中的因素。潜在的非结核相关PAMPs包括革兰氏阴性菌外膜的脂多糖（LPS）、肽聚糖、脂磷壁酸、细菌DNA、病毒DNA/RNA、几丁质、鞭毛蛋白、富含亮氨酸重复序列（LRR）、酵母细胞壁中的甘露聚糖以及微生物HSPs。此外，外源性非有机抗原如金属、二氧化硅、纹身中含/不含铝的颜料、农药和花粉也被认为是结节病的潜在病因。气道暴露于多种感染性和非感染性因子在结节病的发病机制中可能很重要。本综述提供了PRRs和DAMPs在结节病发病机制中作用的最新信息。
