TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models.

IF 4.7 3区 医学 Q2 IMMUNOLOGY Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-10-15 DOI:10.1159/000541819
Zhiguo Gong, Wei Mao, Jiamin Zhao, Peipei Ren, Zhuoya Yu, Yunjie Bai, Chao Wang, Yuze Liu, Shuang Feng, Surong Hasi
{"title":"TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models.","authors":"Zhiguo Gong, Wei Mao, Jiamin Zhao, Peipei Ren, Zhuoya Yu, Yunjie Bai, Chao Wang, Yuze Liu, Shuang Feng, Surong Hasi","doi":"10.1159/000541819","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Escherichia coli (E. coli) is a significant commensal gram-negative bacterium that can give rise to various diseases. The roles of Toll-like receptor 2 (TLR2) and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in sepsis induced by E. coli infection remain unclear.</p><p><strong>Methods: </strong>In vivo, we investigated differences in mortality, production of inflammatory mediators, organ damage, neutrophil count, and bacterial load during E. coli infection in C57BL/6J mice, as well as in mice deficient in TLR2 or NLRP3. In vitro, we investigated the impact of E. coli on the activation of TLR2 and NLRP3 in macrophages and the influence of TLR2 and NLRP3 on the activation of inflammatory signaling pathways and the secretion of inflammatory mediators in macrophages induced by E. coli infection.</p><p><strong>Results: </strong>TLR2-deficient (TLR2-/-) and NLRP3-deficient (NLRP3-/-) mice exhibit significantly increased mortality and organ damage after E. coli infection. These mice also show elevated levels of TNF-α and IL-10 in serum and peritoneal lavage fluid. Additionally, TLR2-/- and NLRP3-/- mice display heightened neutrophil recruitment and increased bacterial load in the blood. Furthermore, macrophages from these mice demonstrate a significant reduction in the activation of the MAPK signaling pathway.</p><p><strong>Conclusion: </strong>TLR2 and NLRP3 play crucial roles in modulating inflammatory mediator expression, immune cell recruitment, and bactericidal activity, thereby preventing excessive tissue damage and reducing mortality in E. coli-induced sepsis.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548895/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Innate Immunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000541819","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/15 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: Escherichia coli (E. coli) is a significant commensal gram-negative bacterium that can give rise to various diseases. The roles of Toll-like receptor 2 (TLR2) and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in sepsis induced by E. coli infection remain unclear.

Methods: In vivo, we investigated differences in mortality, production of inflammatory mediators, organ damage, neutrophil count, and bacterial load during E. coli infection in C57BL/6J mice, as well as in mice deficient in TLR2 or NLRP3. In vitro, we investigated the impact of E. coli on the activation of TLR2 and NLRP3 in macrophages and the influence of TLR2 and NLRP3 on the activation of inflammatory signaling pathways and the secretion of inflammatory mediators in macrophages induced by E. coli infection.

Results: TLR2-deficient (TLR2-/-) and NLRP3-deficient (NLRP3-/-) mice exhibit significantly increased mortality and organ damage after E. coli infection. These mice also show elevated levels of TNF-α and IL-10 in serum and peritoneal lavage fluid. Additionally, TLR2-/- and NLRP3-/- mice display heightened neutrophil recruitment and increased bacterial load in the blood. Furthermore, macrophages from these mice demonstrate a significant reduction in the activation of the MAPK signaling pathway.

Conclusion: TLR2 and NLRP3 play crucial roles in modulating inflammatory mediator expression, immune cell recruitment, and bactericidal activity, thereby preventing excessive tissue damage and reducing mortality in E. coli-induced sepsis.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
TLR2 和 NLRP3 在大肠埃希菌感染诱发的小鼠模型败血症中发挥调节作用。
引言 大肠杆菌(E. coli)是一种重要的革兰氏阴性共生菌,可引发多种疾病。Toll 样受体 2(TLR2)和含 NLR pyrin 结构域的炎性体 3(NLRP3)在大肠杆菌感染诱导的败血症中的作用仍不清楚。方法 在体内,我们研究了 C57BL/6J 小鼠以及 TLR2 或 NLRP3 缺陷小鼠感染大肠杆菌期间死亡率、炎症介质产生、器官损伤、中性粒细胞计数和细菌负荷的差异。在体外,我们研究了大肠杆菌对巨噬细胞中 TLR2 和 NLRP3 激活的影响,以及 TLR2 和 NLRP3 对大肠杆菌感染诱导的巨噬细胞炎症信号通路激活和炎症介质分泌的影响。结果 TLR2 缺失(TLR2-/-)和 NLRP3 缺失(NLRP3-/-)的小鼠在感染大肠杆菌后死亡率和器官损伤显著增加。这些小鼠血清和腹腔灌洗液(PLF)中的 TNF-α 和 IL-10 水平也有所升高。此外,TLR2-/- 和 NLRP3-/- 小鼠表现出中性粒细胞募集增加、血液中细菌负荷增加。此外,这些小鼠的巨噬细胞显示出 MAPK 信号通路的激活显著减少。结论 TLR2 和 NLRP3 在调节炎症介质表达、免疫细胞募集和杀菌活性方面起着至关重要的作用,从而防止大肠杆菌诱导的败血症造成过度的组织损伤并降低死亡率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
期刊最新文献
C4b-Binding Protein and Factor H Inhibit Inflammasome Activation during Group A Streptococci Infection in Human Cells. Inhibition of WNK kinases in NK cells disrupts cellular osmoregulation and control of tumor metastasis. Stat3 regulates developmental hematopoiesis and impacts myeloid cell function via canonical and non-canonical modalities. Hydrogen peroxide is responsible for the cytotoxic effects of Streptococcus pneumoniae on primary microglia in the absence of pneumolysin. Association of Vitamin D with Severity and Outcome of COVID-19: Clinical and Experimental Evidence.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1