a Department of Clinical Sciences, Lund, Division of Infection Medicine , Lund University , Lund , Sweden.
b Centro de Biotecnologia, Instituto Butantan , Avenida Vital Brazil, São Paulo , SP , Brazil.
Virulence. 2018 Jan 1;9(1):414-425. doi: 10.1080/21505594.2017.1407484.
Leptospirosis is a widespread zoonotic and neglected infectious disease of human and veterinary concern that is caused by pathogenic Leptospira species. After entrance in the host, pathogenic leptospires evade the host natural defense mechanisms in order to propagate and disseminate to multiple organs. Myeloperoxidase is an enzyme stored in neutrophils azurophilic granules, and is released upon neutrophil activation to produce mainly hypochlorous acid, a strong oxidant and potent antimicrobial agent. In the present investigation, we studied the modulation of myeloperoxidase activity by L. interrogans serovar Copenhageni. We show that leptospires and their culture supernatants are able to inhibit both peroxidase and chlorination activities of myeloperoxidase, without interfering with neutrophil degranulation. By leptospiral outer membrane protein extraction and fractionation, we identified the proteins LipL21 and LipL45 as myeloperoxidase inhibitors, constituting new Leptospira virulence factors. Accordingly, we propose a function for the protein LipL21, one of the most expressed leptospiral outer membrane proteins. Our results show a novel innate immune evasion mechanism by which leptospires interfere with the host response in order to cope with the host oxidative stress and efficiently achieve dissemination and colonization.
钩端螺旋体病是一种广泛存在的人畜共患和被忽视的传染病，由致病性钩端螺旋体引起。进入宿主后，致病性钩端螺旋体会逃避宿主的天然防御机制，以便繁殖并传播到多个器官。髓过氧化物酶是一种储存在中性粒细胞嗜苯胺蓝颗粒中的酶，在中性粒细胞被激活时释放，主要产生次氯酸，这是一种强氧化剂和有效的抗菌剂。在本研究中，我们研究了钩端螺旋体血清群哥本哈根对髓过氧化物酶活性的调节。我们发现钩端螺旋体及其培养上清液能够抑制髓过氧化物酶的过氧化物酶和氯化活性，而不干扰中性粒细胞脱颗粒。通过钩端螺旋体外膜蛋白提取和分级，我们确定了 LipL21 和 LipL45 这两种蛋白为髓过氧化物酶抑制剂，构成了新的钩端螺旋体毒力因子。因此，我们提出了一种蛋白 LipL21 的功能，它是表达最丰富的钩端螺旋体外膜蛋白之一。我们的结果显示了一种新的先天免疫逃避机制，通过这种机制，钩端螺旋体干扰宿主的反应，以应对宿主的氧化应激，并有效地实现传播和定植。
