Kappagoda Chamila, Senavirathna Indika, Agampodi Thilini, Agampodi Suneth Buddhika
Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Anuradhapura, Sri Lanka.
Department of Biochemistry, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Anuradhapura, Sri Lanka.
PLoS One. 2024 Dec 27;19(12):e0312466. doi: 10.1371/journal.pone.0312466. eCollection 2024.
The involvement of Toll-like receptor 2 (TLR2) in leptospirosis is poorly understood. Our systematic review examined its role across in-vitro, in-vivo, ex-vivo, and human studies. Original articles published in English up to January 2024, exploring the role of TLR2 during leptospirosis, were selected from databases including PubMed, Web of Science, Scopus, Trip, and Google Scholar. Cochrane guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed by this systematic review. The National Institute of Health Quality Assessment tool, Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool, and Office of Health Assessment and Translation extended tool were used to assess the risk of bias of the studies. Out of 2458 studies retrieved, 35 were selected for the systematic review. These comprised 3 human, 17 in-vitro, 5 in-vivo, 3 ex-vivo, and 7 studies with combined experimental models. We assessed the direct TLR2 expression and indirect TLR2 involvement via the secretion/mRNA expression of immune effectors during leptospirosis. Notably, we observed the secretion/mRNA expression of several cytokines (IL6, IL8, IL-1β, TNFα, IFNγ, IL10, CCL2/MCP-1, CCL10, COX2, CXCL1/KC, CXCL2/MIP2) and immune effectors (hBD2, iNOS, Fibronectin, Oxygen, and Nitrogen reactive species) as key aspects of host TLR2 responses during leptospirosis. Even though increased TLR2 expression in in-vivo and in-vitro studies was evident, human studies reported mixed results showing that the postulated effect of TLR2 response based on other studies may not be valid for human leptospirosis. Besides the role of TLR2 in response to leptospirosis, the involvement of TLR4 and TLR5 was identified in in-vitro and in-vivo studies. TLR2 expression is inconclusive during human leptospirosis and further studies are needed to examine the immune effector regulation, through TLR2 for mitigating the harmful effects and promoting effective immune responses.
Toll样受体2（TLR2）在钩端螺旋体病中的作用尚不清楚。我们的系统评价研究了其在体外、体内、离体和人体研究中的作用。从包括PubMed、科学网、Scopus、Trip和谷歌学术在内的数据库中选取了截至2024年1月发表的探索TLR2在钩端螺旋体病中作用的英文原创文章。本系统评价遵循Cochrane指南以及系统评价和Meta分析的首选报告项目。使用美国国立卫生研究院质量评估工具、实验动物系统评价中心实验室偏倚风险工具和健康评估与翻译办公室扩展工具来评估研究的偏倚风险。在检索到的2458项研究中，35项被选入系统评价。这些研究包括3项人体研究、17项体外研究、5项体内研究、3项离体研究以及7项采用联合实验模型的研究。我们评估了钩端螺旋体病期间通过免疫效应物的分泌/ mRNA表达对TLR2的直接表达和间接参与情况。值得注意的是，我们观察到几种细胞因子（IL6、IL8、IL-1β、TNFα、IFNγ、IL10、CCL2/MCP-1、CCL10、COX2、CXCL1/KC、CXCL2/MIP2）和免疫效应物（hBD2、iNOS、纤连蛋白、氧和氮反应性物质）的分泌/ mRNA表达是宿主TLR2在钩端螺旋体病期间反应的关键方面。尽管在体内和体外研究中TLR2表达增加是明显的，但人体研究报告的结果不一，表明基于其他研究推测的TLR2反应效应可能不适用于人类钩端螺旋体病。除了TLR2在应对钩端螺旋体病中的作用外，在体外和体内研究中还确定了TLR4和TLR5的参与情况。在人类钩端螺旋体病期间，TLR2表达尚无定论，需要进一步研究以检查通过TLR2调节免疫效应物，以减轻有害影响并促进有效的免疫反应。
