Peptidoglycan mediates Leptospira outer membrane protein Loa22 to toll-like receptor 2 for inflammatory interaction: a novel innate immune recognition.
Peptidoglycan mediates Leptospira outer membrane protein Loa22 to toll-like receptor 2 for inflammatory interaction: a novel innate immune recognition.
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肽聚糖介导钩端螺旋体外膜蛋白 Loa22 与 Toll 样受体 2 的炎症相互作用：一种新型的先天免疫识别。
DOI：
10.1038/s41598-020-79662-8
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发表时间：
2021-01-13
影响因子：
4.6
通讯作者：
Yang CW
中科院分区：
文献类型：
--
作者：
Hsu SH;Chang MY;Lin SM;Ko YC;Chou LF;Tian YC;Hung CC;Yang CW
钩端螺旋体病是由致病性钩端螺旋体引起的一种被忽视的人畜共患病，其致病性依赖于钩端螺旋体的毒力和宿主-病原体相互作用。肾是钩端螺旋体感染的主要器官，可引起肾小管间质性肾炎。钩端螺旋体外膜含有多种毒力因子，其中外膜蛋白A（OmpA）样蛋白（Loa 22）是其毒力所必需的。Pull-down分析表明Loa 22是致病性钩端螺旋体Toll样受体2（TLR 2）的潜在结合候选者。共聚焦显微镜观察TLR 2与Loa 22-LPGN（Leptospira peptidoglycan）复合物的共定位。利用原子力显微镜（AFM）、侧向诱变和酶联免疫吸附试验（ELISA）研究rLoa 22、LPGN和TLR 2之间的亲和力。采用真实的PCR检测细胞因子的表达。Western blot检测下游信号传导组分，分析基因调控作用。两个Loa 22关键残基（Asp 122和Arg 143）的突变减弱了对LPGN的亲和力。观察到rLoa 22-LPGN复合物与TLR 2共定位，并引起炎症反应，包括CXCL 8/IL 8、hCCL 2/MCP-1和hTNF-α。亲和力研究表明，与Loa 22蛋白相比，Loa 22-LPGN复合物提高了对TLR 2的亲和力。TLR 2的下游信号包括p38、ERK和JNK在rLoa 22-LPGN复合物处理下被调节。该研究确定LPGN介导Loa 22和TLR 2之间的相互作用，并诱导下游信号以触发炎症反应。rLoa 22-LPGN-TLR 2复合物揭示了先天免疫系统的新结合机制。
Leptospirosis is an overlooked zoonotic disease caused by pathogenic Leptospira depended on virulence of Leptospira and the host–pathogen interaction. Kidney is the major organ infected by Leptospira which causes tubulointerstitial nephritis. Leptospira outer membrane contains several virulence factors and an outer membrane protein A (OmpA) like protein (Loa22) is essential for virulence. Pull-down assays suggested that Loa22 was a potential Toll-Like Receptor 2 (TLR2) binding candidates from pathogenic Leptospira. Confocal microscopy was employed to observe the co-localization of TLR2 and Loa22-LPGN (Leptospira peptidoglycan) complexes. Atomic force microscopy (AFM), side-directed mutagenesis, and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the affinity between rLoa22, LPGN, and TLR2. Real time PCR was applied to measure the cytokines expression. Downstream signal transduction components were verified by western blot to evaluate the gene regulations. Mutation of two Loa22 key residues (Asp122 and Arg143) attenuated the affinities for LPGN. rLoa22-LPGN complexes were observed to co-localize with TLR2 and provoked inflammatory responses including CXCL8/IL8, hCCL2/MCP-1, and hTNF-α. Affinity studies suggested that Loa22-LPGN complexes elevated the affinity to TLR2 as compared to Loa22 protein. Downstream signals from TLR2 including p38, ERK, and JNK were regulated under rLoa22-LPGN complexes treatments. This study identified LPGN mediates interactions between Loa22 and TLR2 and induces downstream signals to trigger inflammatory responses. rLoa22-LPGN-TLR2 complexes reveal a novel binding mechanism for the innate immune system.
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DOI：
10.4049/jimmunol.0803737
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Liang S;Hosur KB;Lu S;Nawar HF;Weber BR;Tapping RI;Connell TD;Hajishengallis G
通讯作者：
Hajishengallis G
影响因子：
7.3
作者：
Kawasaki T;Kawai T
通讯作者：
Kawai T
影响因子：
4.8
作者：
Brosh, RM;Li, JL;Bohr, VA
通讯作者：
Bohr, VA
影响因子：
4.8
作者：
Hsu, Shen-Hsing;Lo, Yueh-Yu;Pan, Rong-Long
通讯作者：
Pan, Rong-Long
影响因子：
3
作者：
Kattner, Christof;Toussi, Deana N.;Tanabe, Mikio
通讯作者：
Tanabe, Mikio