Institut Pasteur, Microbiology Department, Unité Biologie et Génétique de la Paroi Bactérienne, Paris, France.
CNRS, UMR 2001 Microbiologie intégrative et Moléculaire, Paris, France.
Front Immunol. 2020 Oct 6;11:571816. doi: 10.3389/fimmu.2020.571816. eCollection 2020.
The spirochetal bacteria spp. are causative agents of leptospirosis, a globally neglected and reemerging zoonotic disease. Infection with these pathogens may lead to an acute and potentially fatal disease but also to chronic asymptomatic renal colonization. Both forms of disease demonstrate the ability of leptospires to evade the immune response of their hosts. In this review, we aim first to recapitulate the knowledge and explore the controversial data about the opsonization, recognition, intracellular survival, and killing of leptospires by scavenger cells, including platelets, neutrophils, macrophages, and dendritic cells. Second, we will summarize the known specificities of the recognition or escape of leptospire components (the so-called microbial-associated molecular patterns; MAMPs) by the pattern recognition receptors (PRRs) of the Toll-like and NOD-like families. These PRRs are expressed by phagocytes, and their stimulation by MAMPs triggers pro-inflammatory cytokine and chemokine production and bactericidal responses, such as antimicrobial peptide secretion and reactive oxygen species production. Finally, we will highlight recent studies suggesting that boosting or restoring phagocytic functions by treatments using agonists of the Toll-like or NOD receptors represents a novel prophylactic strategy and describe other potential therapeutic or vaccine strategies to combat leptospirosis.
螺旋体细菌 spp. 是钩端螺旋体病的病原体,这是一种被全球忽视且重新出现的人畜共患疾病。感染这些病原体可能导致急性和潜在致命的疾病,但也可能导致慢性无症状的肾脏定植。这两种形式的疾病都表明了钩端螺旋体逃避宿主免疫反应的能力。在这篇综述中,我们首先旨在回顾关于吞噬细胞(包括血小板、中性粒细胞、巨噬细胞和树突状细胞)对钩端螺旋体的调理作用、识别、细胞内存活和杀伤的知识,并探讨有争议的数据。其次,我们将总结已知的钩端螺旋体成分(所谓的微生物相关分子模式;MAMPs)被 Toll 样和 NOD 样家族的模式识别受体(PRRs)识别或逃避的特异性。这些 PRRs 由吞噬细胞表达,其 MAMPs 的刺激会引发促炎细胞因子和趋化因子的产生以及杀菌反应,如抗菌肽的分泌和活性氧物质的产生。最后,我们将强调最近的研究表明,使用 Toll 样或 NOD 受体激动剂治疗来增强或恢复吞噬功能代表了一种新的预防策略,并描述了其他潜在的治疗或疫苗策略来对抗钩端螺旋体病。