Fraga Tatiana Rodrigues, Isaac Lourdes, Barbosa Angela Silva
Laboratory of Complement, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil.
Laboratory of Bacteriology, Instituto Butantan , São Paulo , Brazil.
Front Immunol. 2016 Dec 21;7:623. doi: 10.3389/fimmu.2016.00623. eCollection 2016.
Leptospirosis is a neglected infectious disease caused by spirochetes from the genus . Pathogenic microorganisms, notably those which reach the blood circulation such as , have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor survival and multiplication in the host.
钩端螺旋体病是一种由钩端螺旋体属螺旋体引起的被忽视的传染病。致病微生物，尤其是那些进入血液循环的微生物，如[具体微生物名称未给出]，已经进化出多种策略来逃避宿主补体系统，而补体系统对先天免疫和获得性免疫都很重要。[具体微生物名称未给出]通过以下方式避免补体介导的杀伤：（i）招募宿主补体调节蛋白；（ii）获取能在细菌表面切割补体蛋白的宿主蛋白酶；以及（iii）分泌能使周围环境中的补体蛋白失活的蛋白酶。宿主可溶性补体调节蛋白的招募包括获取因子H（FH）和类FH-1（替代途径）、C4b结合蛋白（C4BP）（经典途径和凝集素途径）以及玻连蛋白（Vn）（末端途径）。一旦与钩端螺旋体表面结合，FH和C4BP分别在C3b和C4b的切割中保留因子I的辅因子活性。钩端螺旋体获取Vn可能通过阻断C9聚合而导致末端途径抑制。第二种逃避机制在于纤溶酶原（PLG）与钩端螺旋体表面结合。在宿主激活剂存在的情况下，PLG转化为具有酶活性的纤溶酶，纤溶酶能够在病原体表面降解C3b、C4b和C5。钩端螺旋体逃避补体系统的第三种策略是主动分泌蛋白酶。致病性钩端螺旋体而非腐生性钩端螺旋体能够分泌金属蛋白酶，这些金属蛋白酶可切割C3（补体中心分子）、因子B（替代途径）以及C4和C2（经典途径和凝集素途径）。本综述的目的是全面探讨这些补体逃避机制，这些机制共同作用有利于[具体微生物名称未给出]在宿主体内的存活和繁殖。
