Blood treatment of Lyme borreliae demonstrates the mechanism of CspZ-mediated complement evasion to promote systemic infection in vertebrate hosts
Blood treatment of Lyme borreliae demonstrates the mechanism of CspZ-mediated complement evasion to promote systemic infection in vertebrate hosts
复制标题
莱姆疏螺旋体的血液处理证明了 CspZ 介导的补体逃逸促进脊椎动物宿主全身感染的机制
DOI：
10.1111/cmi.12998
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发表时间：
2019
影响因子：
3.4
通讯作者：
Lin, Yi-Pin
中科院分区：
文献类型：
--
作者：
Marcinkiewicz, Ashley L.;Dupuis, Alan P.;Zamba-Campero, Maxime;Nowak, Nancy;Kraiczy, Peter;Ram, Sanjay;Kramer, Laura D.;Lin, Yi-Pin
莱姆病由伯氏疏螺旋体引起，是美国和欧洲最常见的病媒传播疾病。螺旋体通过蜱从哺乳动物和鸟类宿主传播给人类。蜱叮咬后，螺旋体定殖宿主皮肤，然后通过造血途径传播到各种器官，这一过程需要这种病原体逃避宿主补体，一种先天免疫防御系统。CspZ是一种螺旋体表面蛋白，通过与补体调节因子H（FH）结合，在体外促进对补体介导的杀伤的抵抗。CspZ在体外培养的螺旋体中或在体内感染起始期间的低表达水平一直是描述这种蛋白在发病机制中的作用的主要障碍。在这里，我们表明，与人类血液治疗伯氏疏螺旋体诱导CspZ的生产和增强抵抗补体。相比之下，acspZ缺陷型突变体和表达FH非结合CspZ变体的菌株在引起菌血症和定殖小鼠或鹌鹑组织的能力方面受损;然而，这些突变体的毒力在补体C3缺陷型小鼠中恢复。这些新的发现表明FH与CspZ的结合促进了体内伯氏疏螺旋体的补体逃避，并促进了脊椎动物宿主的全身感染。
Lyme disease, caused by the spirocheteBorrelia burgdorferi, is the most common vector‐borne disease in the United States and Europe. The spirochetes are transmitted from mammalian and avian reservoir hosts to humans via ticks. Following tick bites, spirochetes colonize the host skin and then disseminate haematogenously to various organs, a process that requires this pathogen to evade host complement, an innate immune defence system. CspZ, a spirochete surface protein, facilitates resistance to complement‐mediated killing in vitro by binding to the complement regulator, factor H (FH). Low expression levels of CspZ in spirochetes cultivated in vitro or during initiation of infection in vivo have been a major hurdle in delineating the role of this protein in pathogenesis. Here, we show that treatment ofB. burgdorferiwith human blood induces CspZ production and enhances resistance to complement. By contrast, acspZ‐deficient mutant and a strain that expressed an FH‐nonbinding CspZ variant were impaired in their ability to cause bacteraemia and colonize tissues of mice or quail; virulence of these mutants was however restored in complement C3‐deficient mice. These novel findings suggest that FH binding to CspZ facilitatesB. burgdorfericomplement evasion in vivo and promotes systemic infection in vertebrate hosts.