Clinical Microbiology, Department of Translational Medicine, Faculty of Medicine, Lund University, Malmö, Sweden.
FEBS Lett. 2020 Aug;594(16):2586-2597. doi: 10.1002/1873-3468.13758. Epub 2020 Mar 9.
All infective bacterial species need to conquer the innate immune system in order to colonize and survive in their hosts. The human respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis are no exceptions and have developed sophisticated mechanisms to evade complement-mediated killing. Both bacterial species carry lipooligosaccharides preventing complement attacks and attract and utilize host complement regulators C4b binding protein and factor H to inhibit the classical and alternative pathways of complement activation, respectively. In addition, the regulator of the terminal pathway of complement activation, vitronectin, is hijacked by both bacteria. An array of different outer membrane proteins (OMP) in H. influenzae and M. catarrhalis simultaneously binds complement regulators, but also plasminogen. Several of the bacterial complement-binding proteins are important adhesins and contain highly conserved regions for interactions with the host. Thus, some of the OMP are viable targets for new therapeutics, including vaccines aimed at preventing respiratory tract diseases such as otitis media in children and exacerbations in patients suffering from chronic obstructive pulmonary disease.
所有感染性细菌物种都需要征服先天免疫系统,才能在宿主体内定植和生存。人类呼吸道病原体流感嗜血杆菌和卡他莫拉菌也不例外,它们已经发展出了复杂的机制来逃避补体介导的杀伤。这两种细菌都携带脂寡糖,防止补体攻击,并吸引和利用宿主补体调节蛋白 C4b 结合蛋白和因子 H,分别抑制补体激活的经典途径和替代途径。此外,补体激活终末途径的调节蛋白,即玻连蛋白,也被这两种细菌劫持。流感嗜血杆菌和卡他莫拉菌的一系列不同的外膜蛋白 (OMP) 既能结合补体调节蛋白,也能结合纤溶酶原。几种细菌补体结合蛋白是重要的黏附素,含有与宿主相互作用的高度保守区域。因此,一些 OMP 是新疗法的可行靶点,包括旨在预防儿童中耳炎和慢性阻塞性肺疾病患者恶化等呼吸道疾病的疫苗。