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人纤溶酶相关致病性钩端螺旋体免疫逃逸活性的体外证据。

In vitro evidence for immune evasion activity by human plasmin associated to pathogenic Leptospira interrogans.

机构信息

Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, Brazil.

出版信息

Microb Pathog. 2011 Nov;51(5):360-5. doi: 10.1016/j.micpath.2011.06.008. Epub 2011 Jul 23.

DOI:10.1016/j.micpath.2011.06.008
PMID:21802507
Abstract

Leptospirosis is a widespread re-emerging zoonosis of human and veterinary concern. It has been shown that virulent leptospires protect themselves against the host's innate immune system, a strategy that allows the bacteria to reach immunologically safe environments. Although extensive studies on host-pathogen interactions have been performed, little is known on how leptospires deal with host immune attack. In a previous work, we demonstrated the ability of leptospires to bind human plasminogen (PLG), that after treatment with activators, conferred plasmin (PLA) activity on the bacteria surface. In this study, we show that the PLA activity associated to the outer surface of Leptospira could interfere with the host immune attack by conferring some evasion advantage during infection. We demonstrate that PLA-coated leptospires interfere with complement C3b and IgG depositions on the bacterial surface, probably through the degradation of these components, thus diminishing opsonization process. Similar decrease on the deposition was observed when normal and immune sera from patients diagnosed with leptospirosis were employed as a source of IgG. We believe that decreasing opsonization by PLA generation might be an important aspect of the leptospiral immune escape strategy and survival. To our knowledge, this is the first proteolytic activity of plasmin associated-Leptospira related to anti-opsonic properties reported to date.

摘要

钩端螺旋体病是一种广泛存在的人畜共患再发性传染病。已经表明,毒力钩端螺旋体会保护自己免受宿主固有免疫系统的攻击,这种策略使细菌能够到达免疫安全的环境。尽管已经对宿主-病原体相互作用进行了广泛的研究,但对于钩端螺旋体如何应对宿主免疫攻击知之甚少。在之前的一项工作中,我们证明了钩端螺旋体能够结合人纤溶酶原(PLG),经激活剂处理后,赋予细菌表面纤溶酶(PLA)活性。在本研究中,我们表明与 Leptospira 外表面相关的 PLA 活性可以通过在感染过程中赋予一些逃避优势来干扰宿主免疫攻击。我们证明 PLA 包被的钩端螺旋体可以干扰补体 C3b 和 IgG 在细菌表面的沉积,可能通过降解这些成分,从而减少调理作用。当使用诊断为钩端螺旋体病的患者的正常和免疫血清作为 IgG 来源时,观察到类似的沉积减少。我们认为通过 PLA 生成减少调理作用可能是钩端螺旋体免疫逃避策略和存活的一个重要方面。据我们所知,这是迄今为止报道的与抗调理特性相关的纤溶酶相关 Leptospira 的第一个蛋白水解活性。

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