Department of Medicine, Pulmonary Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Eur J Immunol. 2024 Nov;54(11):e2350814. doi: 10.1002/eji.202350814. Epub 2024 Aug 27.
Infections are one of the most significant healthcare and economic burdens across the world as underscored by the recent coronavirus pandemic. Moreover, with the increasing incidence of antimicrobial resistance, there is an urgent need to better understand host-pathogen interactions to design effective treatment strategies. The complement system is a key arsenal of the host defense response to pathogens and bridges both innate and adaptive immunity. However, in the contest between pathogens and host defense mechanisms, the host is not always victorious. Pathogens have evolved several approaches, including co-opting the host complement regulators to evade complement-mediated killing. Furthermore, deficiencies in the complement proteins, both genetic and therapeutic, can lead to an inefficient complement-mediated pathogen eradication, rendering the host more susceptible to certain infections. On the other hand, overwhelming infection can provoke fulminant complement activation with uncontrolled inflammation and potentially fatal tissue and organ damage. This review presents an overview of critical aspects of the complement-pathogen interactions during infection and discusses perspectives on designing therapies to mitigate complement dysfunction and limit tissue injury.
感染是全球范围内最重大的医疗保健和经济负担之一，最近的冠状病毒大流行更是凸显了这一点。此外，随着抗菌药物耐药性的不断增加，迫切需要更好地了解宿主-病原体相互作用，以设计有效的治疗策略。补体系统是宿主防御反应针对病原体的关键武器库，连接先天免疫和适应性免疫。然而，在病原体和宿主防御机制的较量中，宿主并非总是胜利者。病原体已经进化出几种方法，包括利用宿主补体调节剂来逃避补体介导的杀伤。此外，补体蛋白的遗传和治疗缺陷会导致补体介导的病原体清除效率降低，使宿主更容易感染某些感染。另一方面，过度的感染会引发补体的剧烈激活，导致失控的炎症和潜在的致命组织和器官损伤。本综述介绍了感染过程中补体-病原体相互作用的关键方面，并讨论了设计治疗方法以减轻补体功能障碍和限制组织损伤的观点。
