Direct interaction between Urease B of Helicobacter pylori and TLR2 negatively regulates immune fucntions of macrophages
10.3760/cma.j.cn112309-20200730-00380
- VernacularTitle:幽门螺杆菌尿素酶B通过与TLR2结合负向调控巨噬细胞免疫功能
- Author:
Zhichao LI
1
;
Xin SHEN
;
Chunhui YUAN
;
Jun WANG
;
Yun XIANG
;
Qinzhen CAI
Author Information
1. 华中科技大学同济医学院附属武汉儿童医院风湿免疫科 430016
- Keywords:
UreB;
TLR2;
Macrophages;
Antigen presentation
- From:
Chinese Journal of Microbiology and Immunology
2021;41(7):507-515
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the regulatory role and potential mechanism of Urease B(UreB) on macrophages.Methods:Bone marrow-derived macrophages (M0) were stimulated by recombinant UreB protein and then flowcytometry and ELISA were used to detect the apoptosis, polarization and antigen presentation-related biomarkers expression. CD4 + T cell co-culture assay, CFSE stain and flowcytometry were used to evaluate the impacts of UreB on antigen presentation capacity of macrophages. Truncated UreB protein, NanoBiT assay and co-immunoprecipitation were used to identify the binding sites of UreB to TLR2. Results:UreB promoted apoptosis and skewed macrophages from M1 to M2 in the presence of M1-inducer LPS. Moreover, UreB inhibited the expression of antigen presentation biomarkers, MHCⅡ and CD86 on macrophages, and further inhibited the proliferation and IFN-γ expression of CD4 + T cells. Molecular analyses revealed that the binding between seven carboxy-terminal amino acid residues of UreB and TLR2 were required for the UreB-mediated inhibitory effects. Conclusions:The findings in this study demonstrate that UreB mainly depends on the binding between seven carboxy-terminal amino acid residues and TLR2 to perform immune-suppressive activities, and which may provide valuable information for the design and optimization of UreB-based vaccines against Helicobacter pylori infection.
