Pathogenesis of Acanthamoeba Keratitis
Pathogenesis of Acanthamoeba Keratitis
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DOI：
10.1016/s1542-0124(12)70071-x
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发表时间：
2010-04-01
期刊：
影响因子：
6.4
通讯作者：
Panjwani, Noorjahan
中科院分区：
文献类型：
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作者：
Panjwani, Noorjahan
阿米巴角膜炎（AK）是一种严重的角膜感染。目前，这种疾病的诊断并不简单，治疗要求很高。虽然接触透镜配戴是AK的主要风险因素，但越来越多的人认为阿米巴原虫是非接触透镜配戴者角膜炎的重要原因。感染发病机制的第一个关键步骤是微生物粘附到宿主组织表面。阿米巴表达一种主要的毒力蛋白，甘露糖结合蛋白（MBP），它介导阿米巴粘附到角膜表面。MBP是一种具有典型细胞表面受体特征的跨膜蛋白。在MBP介导的与宿主细胞的粘附之后，阿米巴产生一种接触依赖性金属蛋白酶和几种接触非依赖性丝氨酸蛋白酶。这些蛋白酶协同工作以产生有效的细胞病变效应（CPE），包括杀死宿主细胞、上皮基底膜和下面的基质的降解以及渗透到角膜的更深层中。在仓鼠动物模型中，用重组MBP进行口服免疫可防止AK，并且这种保护与受保护动物泪液中抗MBP IgA水平的增加有关。正常人泪液含有抗阿米巴MBP的IgA抗体，其可能通过抑制寄生虫对宿主细胞的粘附来提供保护。事实上，在体外CPE测定中，即使是低浓度的泪液（每毫升培养基10 μ L未稀释的泪液）也几乎完全抑制阿米巴诱导的CPE。除了粘附抑制，IgA介导的保护，人泪液还含有IgA非依赖性因子，通过抑制细胞毒性蛋白酶的活性提供对阿米巴诱导的CPE的保护。人泪液的CPE抑制因子的表征应导致更好地理解宿主组织抵抗感染的机制，并有助于解码易患阿米巴感染的情况。
Acanthamoeba keratitis (AK) is a serious infection of the cornea. At present, diagnosis of the disease is not straightforward and treatment is very demanding. While contact lens wear is the leading risk factor for AK, Acanthamoeba parasites are increasingly recognized as an important cause of keratitis in non-contact lens wearers. The first critical step in the pathogenesis of infection is the adhesion of the microbe to the surface of the host tissues. Acanthamoebae express a major virulence protein, the mannose-binding protein (MBP), which mediates the adhesion of amoebae to the surface of the cornea. The MBP is a transmembrane protein with characteristics of a typical cell surface receptor. Subsequent to the MBP-mediated adhesion to host cells, the amoebae produce a contact-dependent metalloproteinase and several contact-independent serine proteinases. These proteinases work in concert to produce a potent cytopathic effect (CPE) involving killing of the host cells, degradation of epithelial basement membrane and underlying stromal matrix, and penetration into the deeper layers of the cornea. In the hamster animal model, oral immunization with the recombinant MBP protects against AK, and this protection is associated with an increased level of anti-MBP IgA in tears of protected animals. Normal human tear fluid contains IgA antibodies against Acanthamoeba MBP that is likely to provide protection by inhibiting the adhesion of parasites to host cells. Indeed, in in vitro CPE assays, even a low concentration of tears (10 mu L of undiluted tears per milliliter of media) almost completely inhibits Acanthamoeba-induced CPE. In addition to adherence-inhibiting, IgA-mediated protection, human tears also contain IgA-independent factors that provide protection against Acanthamoeba-induced CPE by inhibiting the activity of cytotoxic proteinases. Characterization of the CPE-Inhibitory factors of human tears should lead to a better understanding of the mechanism by which the tissues of the host resist the infection and also help decode circumstances that predispose to Acanthamoeba infections.