Leptospirosis Pathophysiology: Into the Storm of Cytokines.
Leptospirosis Pathophysiology: Into the Storm of Cytokines.
复制标题
钩端螺旋体病理生理学：进入细胞因子的风暴。
DOI：
10.3389/fcimb.2018.00204
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发表时间：
2018
影响因子：
5.7
通讯作者：
Matsui M
中科院分区：
文献类型：
--
作者：
Cagliero J;Villanueva SYAM;Matsui M
钩端螺旋体病是一种被忽视的热带人畜共患病，由钩端螺旋体属的致病螺旋体引起。受感染的宿主动物，通常是小鼠和大鼠，没有症状，在它们的肾小管中携带病原体，并在它们的尿液中排出致病性螺旋体，污染环境。人类是致病性钩端螺旋体的偶然宿主。大多数人类感染是轻微的或无症状的。然而，10%的人类钩端螺旋体病病例发展为严重形式，包括高钩端螺旋体血症、多器官损伤和死亡率显著增加，这可能与败血症样表型有关。在感染期间，炎症反应的触发，特别是通过细胞因子的产生，对于病原体的早期消除是必不可少的。然而，不受控制的细胞因子产生可导致细胞因子风暴过程，随后是免疫麻痹状态，其可导致败血症和相关器官衰竭。在这篇综述中，将讨论在易感宿主中严重钩端螺旋体病的发展中细胞因子风暴和随后的免疫麻痹的参与。还将检查主要促炎细胞因子在组织病变和全身炎症反应发展中的潜在作用，以及抗炎细胞因子在导致有害免疫抑制级联反应发生中的作用。将纳入比较易感和耐药小鼠模型的研究数据。最后，将简要讨论细胞因子用于治疗目的或作为钩端螺旋体病严重程度的生物标志物。
Leptospirosis is a neglected tropical zoonosis caused by pathogenic spirochetes of the genus Leptospira. Infected reservoir animals, typically mice and rats, are asymptomatic, carry the pathogen in their renal tubules, and shed pathogenic spirochetes in their urine, contaminating the environment. Humans are accidental hosts of pathogenic Leptospira. Most human infections are mild or asymptomatic. However, 10% of human leptospirosis cases develop into severe forms, including high leptospiremia, multi-organ injuries, and a dramatically increased mortality rate, which can relate to a sepsis-like phenotype. During infection, the triggering of the inflammatory response, especially through the production of cytokines, is essential for the early elimination of pathogens. However, uncontrolled cytokine production can result in a cytokine storm process, followed by a state of immunoparalysis, which can lead to sepsis and associated organ failures. In this review, the involvement of cytokine storm and subsequent immunoparalysis in the development of severe leptospirosis in susceptible hosts will be discussed. The potential contribution of major pro-inflammatory cytokines in the development of tissue lesions and systemic inflammatory response, as well as the role of anti-inflammatory cytokines in contributing to the onset of a deleterious immunosuppressive cascade will also be examined. Data from studies comparing susceptible and resistant mouse models will be included. Lastly, a concise discussion on the use of cytokines for therapeutic purposes or as biomarkers of leptospirosis severity will be provided.