莱姆病螺旋体的转移感染和致病机制

本文主要就莱姆病螺旋体从蜱到宿主动物的转移感染以及在宿主体内存活并致病的机制进行了的阐述,包括螺旋体在蜱内定居以及感染宿主动物过程中蛋白的变化及作用;螺旋体在宿主体内致病的各种机制(病原体本身的作用、免疫逃避、细胞因子的作用、自身免疫)。     

Perspectives on "chronic Lyme disease"

There is much controversy about the treatment of Lyme disease with respect to 2 poorly defined entities: “chronic Lyme disease” and “posttreatment Lyme disease syndrome.” In the absence of direct evidence that these conditions are the result of a persistent infection, some mistakenly advocate extended antibiotic therapy (≥6 months), which can do great harm and has resulted in at least 1 death. The purpose of this brief report is to review what is known from clinical research about these conditions to assist both practicing physicians and lawmakers in making sound and safe decisions with respect to treatment.     

Interaction of spirochetes with the host fibrinolytic system and potential roles in pathogenesis

Abstract

The pathogenic spirochetes Borrelia burgdorferi, B. hermsii, B. recurrentis, Treponema denticola and Leptospira spp. are the etiologic agents of Lyme disease, relapsing fever, periodontitis and leptospirosis, respectively. Lyme borreliosis is a multi-systemic disorder and the most prevalent tick-borne disease in the northern hemisphere. Tick-borne relapsing fever is persistent in endemic areas worldwide, representing a significant burden in some African regions. Periodontal disease, a chronic inflammatory disorder that often leads to tooth loss, is caused by several potential pathogens found in the oral cavity including T. denticola. Leptospirosis is considered the most widespread zoonosis, and the predominant human disease in tropical, undeveloped regions. What these diseases have in common is that they are a significant burden to healthcare costs in the absence of prophylactic measures. This review addresses the interaction of these spirochetes with the fibrinolytic system, plasminogen (Plg) binding to the surface of bacteria and the generation of plasmin (Pla) on their surface. The consequences on host–pathogen interactions when the spirochetes are endowed with this proteolytic activity are discussed on the basis of the results reported in the literature. Spirochetes equipped with Pla activity have been shown to degrade extracellular matrix (ECM) components, in addition to digesting fibrin, facilitating bacterial invasion and dissemination. Pla generation triggers the induction of matrix metalloproteases (MMPs) in a cascade of events that enhances the proteolytic capacity of the spirochetes. These activities in concert with the interference exerted by the Plg/Pla on the complement system – helping the bacteria to evade the immune system – should illuminate our understanding of the mechanisms involved in host infection.     

IFA、ELISA和WB用于莱姆病血清学诊断的比较研究

目的比较研究间接免疫荧光试验（IFA）、酶联免疫吸附试验（ELISA）和蛋白免疫印迹试验（WB）3种检测方法对莱姆病血清学的诊断效果。方法收集临床疑似莱姆病患者血清标本及其流行病学和临床资料,分别采用IFA、ELISA和WB进行血清抗伯氏疏螺旋体抗体（IgM和IgG）检测,结合流行病学和临床资料进行综合分析。结果实验共检测莱姆病疑似患者血清398份,ELISA阳性86例,阳性率21.61%,其中IgM阳性27例,IgG阳性59例;IFA阳性82例,阳性率20.60%,其中IgM阳性26例,IgG阳性56例;WB阳性83例,阳性率20.85%,其中IgM阳性31例,IgG阳性52例;并且实验表明,在对于游走性红斑病例的诊断上,WB法阳性率明显高于ELISA和IFA（χ2=6.34,P〈0.05）。结论在莱姆病的实验室诊断中,IFA、ELISA和WB3种方法结合运用,可提高诊断的灵敏性和特异性;WB在排除ELISA和IFA的假阳性结果中有着重要作用。     

莱姆病伯氏疏螺旋体在黑线姬鼠体内垂直传播的证实

我们于1992年在辽宁省桓仁县开展莱姆病动物宿主调查时,从黑线姬鼠的胎鼠肝中分离到1株伯氏疏螺旋体,命名为辽6。该分离株与单克隆抗体H5332、H9724反应良好,与H6831不反应(B31株均反应),分离株与国际标准株B31(分离自美国达敏硬蜱)比较,其抗原性质相似,但不完全相同。从黑线姬鼠的胎鼠中分离到伯氏疏螺旋体为世界首次报告,证明该螺旋体在小型野鼠体内可能存在经胎盘的垂直传播过程,此种传播途径在维持莱姆病自然疫源地的连续存在方面具有一定意义。     

我国部分地区蜱中莱姆病螺旋体的检测与基因分型研究

目的 对我国部分地区的多种蜱类进行莱姆病螺旋体的检测和基因分型。方法 选择我国黑龙江、吉林和浙江省部分林区为调查点，采集当地蜱类，用巢式PCR法进行检测，阳性产物进行限制性片段长度多态性（RFLP）分析和单链构象多态性（SSCP）分析，确定莱姆病螺旋体的基因型。结果 共检测蜱512只，阳性126只，阳性率24．61％。其中吉林全沟硬蜱带菌率为37．00％，黑龙江全沟硬蜱带菌率为20．87％，浙江长角血蜱带菌率为28．07％。RFLP分析表明，蜱中莱姆病螺旋体包括B．garinii和B．afzelii两种基因型。SSCP分析显示为7种亚型，其中B．garinii分为5个亚型，B．afzelii分为2个亚型。发现有3只蜱同时感染不同基因（亚）型莱姆病螺旋体。结论 证实B．garinii和B．afzelii基因型为我国莱姆病螺旋体的优势基因型，并在我国蜱中发现莱姆病螺旋体不同基因（亚）型的混合感染。     

莱姆病实验动物模型研究

用从我国新疆全沟硬蜱分离培养的莱姆病螺旋体(XS3),实验感染了新西兰白兔、大耳白兔、13号鼠、大白鼠、中国地鼠、金黄地鼠和豚鼠等7种动物。在一只新西兰白兔发现慢性游走性红斑,一只金黄地鼠和一只13号鼠产生关节炎。患病动物都有较高滴度的抗体。这些结果证实。(1)我国全沟硬蜱莱姆病螺旋体具有足够致病的能力;(2)经培养传代的螺旋体的毒力是稳定的,可引起实验动物莱姆病;(3)莱姆病的发病机理可能与免疫应答有关。另外,证实血中螺旋体的浓度较低,持续时间较短。     

Intracellular persistence ofBorrelia burgdorferi in human synovial cells

To investigate ifBorrelia burgdorferi can persist in resident joint cells, an infection model using cell cultures of human synovial cells was established and compared to the interaction ofBorrelia burgdorferi and human macrophages.Borrelia burgdorferi were found attached to the cell surface or folded into the cell membrane of synovial cells analysed by transmission electron and confocal laser scanning microscopy. In contrast to macrophages, morphologically intactBorrelia burgdorferi were found in the cytosol of synovial cells without engulfment by cell membrane folds or phagosomes.Borrelia burgdorferi were isolated from parallel cultures. Treatment with ceftriaxone eradicated extracellularBorrelia burgdorferi, but spirochetes were reisolated after lysis of the synovial cells.Borrelia burgdorferi persisted inside synovial cells for at least 8 weeks. These data suggested thatBorrelia burgdorferi might be able to persist within resident joint cells in vivo.     

Effect of tick saliva on immune interactions between Borrelia afzelii and murine dendritic cells

Interaction between mouse dendritic cells (DCs) and Borrelia afzelii spirochetes was monitored on three different levels: phagocytosis of spirochetes by DCs, production of cytokines by Borrelia-stimulated DCs and the ability of Borrelia-exposed DCs to activate specific CD4+ T lymphocytes. The effect of Ixodes ricinus tick saliva on each of these interactions was examined. Tick saliva was shown to decrease the number of phagocytosing DCs. The ability of Borrelia-exposed DCs to induce both proliferation and IL-2 production by specific CD4+ T cells was significantly reduced by tick saliva. And surprisingly, we have shown an inhibitory effect of tick saliva on the production of both Th1 (TNF-α and IL-6) and Th2 (IL-10) cytokines by DCs. Our data reveal a complex inhibitory effect of tick saliva on Borrelia-DCs interaction.     

Blood donor Borrelia burgdorferi sensu lato seroprevalence and history of tick bites at a northern limit of the vector distribution

In order to study the antibody seroprevalence of the causal agent of Lyme borreliosis, Borrelia burgdorferi sensu lato (s.l.), and the history of tick bites at a geographical distribution limit of Ixodes ricinus, we compared healthy blood donors in geographically extreme regions: the borreliosis‐endemic Vestfold County (59°N) and the region of northern Norway. Blood samples were screened using IgG/VlsE ELISA, and positive/borderline samples were confirmed using C6 ELISA and immunoblot assays. Also, donors completed a questionnaire consisting of several items including the places they have lived, and whether they owned any pets. The seroprevalence was 0.48% (5/1048) in northern Norway and 9.25% (48/519) in Vestfold County. Seven donors (of 1048) had experienced a single tick bite in the southern part of Nordland County (65°N) in northern Norway. This first study on B. burgdorferi s.l. antibody seroprevalence and tick bites on humans and pets in northern Norway showed that the seroprevalence of B. burgdorferi s.l. infection and the risk of tick bite in northern Norway are insignificant; the fact that only five positive IgG samples were detected underscores the very low background seroprevalence. These results suggest that so far I. ricinus has not expanded north of the previously established geographical distribution limit.