Hardy Gail G, Tudor Simone M, St Geme Joseph W
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Methods Mol Med. 2003;71:1-28. doi: 10.1385/1-59259-321-6:01.
To summarize, the pathogenesis of disease due to nontypeable H. influenzae involves multiple steps and the interplay of a number of bacterial and host factors, as shown in Fig. 1. Following entry into the upper respiratory tract, bacteria encounter the mucociliary escalator. The P2 and P5 outer-membrane proteins and probably other factors promote bacterial binding to mucus, and elaboration of LOS causes damage to ciliated cells and impairs mucociliary function. Subsequently, several adhesins, including HMW1 and HMW2, pili, Hia, Hap, and others, mediate direct adherence to nonciliated epithelial cells. Cleavage of IgA1, invasion into cells and the subepithelial space, and phase and antigenic variation facilitate evasion of local immune mechanisms. Binding and uptake of iron and heme allow organisms to persist on the respiratory mucosa despite the relative scarcity of these nutrients. In the setting of a viral infection, allergic disease, or exposure to cigarette smoke, bacteria spread from the nasopharynx to other sites within the respiratory tract and produce symptomatic disease.
综上所述，如图1所示，不可分型流感嗜血杆菌所致疾病的发病机制涉及多个步骤以及多种细菌和宿主因素的相互作用。细菌进入上呼吸道后，会遇到黏液纤毛清除系统。P2和P5外膜蛋白以及可能的其他因素促进细菌与黏液结合，脂寡糖（LOS）的产生会损伤纤毛细胞并损害黏液纤毛功能。随后，包括高分子量蛋白1（HMW1）和高分子量蛋白2（HMW2）、菌毛、流感嗜血杆菌黏附素（Hia）、血凝素蛋白酶（Hap）等在内的多种黏附素介导细菌直接黏附于非纤毛上皮细胞。IgA1的裂解、侵入细胞和上皮下间隙以及相位和抗原变异有助于逃避局部免疫机制。尽管这些营养物质相对稀缺，但铁和血红素的结合与摄取使病原体能够在呼吸道黏膜上持续存在。在病毒感染、过敏性疾病或接触香烟烟雾的情况下，细菌会从鼻咽部扩散到呼吸道内的其他部位并引发症状性疾病。
