A subunit vaccine based on rH-NS induces protection against Mycobacterium tuberculosis infection by inducing the Th1 immune response and activating macrophages | |
Liu, Yuan ; Chen, Suting ; Pan, Bowen ; Guan, Zhu ; Yang, Zhenjun ; Duan, Linfei ; Cai, Hong | |
刊名 | ACTA BIOCHIMICA ET BIOPHYSICA SINICA |
2016 | |
关键词 | tuberculosis rH-NS antigen vaccines adjuvant cytokines APC function TLR2 CYCLIC GMP-AMP COMPLETE GENOME SEQUENCE TOLL-LIKE RECEPTORS C-DI-GMP DIGUANYLIC ACID CELLULOSE SYNTHESIS PROTEIN-KINASE ACETOBACTER-XYLINUM DENDRITIC CELLS CYTOSOLIC DNA |
DOI | 10.1093/abbs/gmw078 |
英文摘要 | Mycobacterium tuberculosis (Mtb) is a Gram-positive pathogen which causes tuberculosis in both animals and humans. All tested rH-NS formulations induced a specific Th1 response, as indicated by increased production of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) by lymphocytes in the spleen of mice which were immunized with rH-NS alone or with rH-NS and the adjuvant cyclic GMP-AMP (cGAMP). Serum from mice immunized with rH-NS with or without adjuvant also had higher levels of IL-12p40 and TNF-alpha, compared with those from control mice immunized with phosphate-buffered saline. Both vaccines increased protective efficacy in mice which were challenged with Mtb H37Rv, as measured by reduced relative CFU counts in the lungs. We found that rH-NS induced the production of TNF-alpha, IL-6, and IL-12p40, which relied on the activation of mitogen-activated protein kinases by stimulating the rapid phosphorylation of ERK1/2, p38, and JNK, and on the activation of transcription factor NF-kappa B in macrophages. Additionally, we also found that rH-NS could interact with TLR2 but not TLR4 in pull-down assays. The rH-NS-induced cytokine production from TLR2-silenced RAW264.7 cells was lower than that from BALB/c macrophages. Prolonged exposure (>24 h) of RAW264.7 cells to rH-NS resulted in a significant enhancement in IFN-gamma-induced MHC II expression, which was not found in shTLR2-treated RAW264.7 cells. These results suggest that rH-NS is a TLR2 agonist which induces the production of cytokines by macrophages and up-regulates macrophage function.; Seeding Grant for Medicine and Life Sciences of Peking University [2014-MB-15]; SCI(E); PubMed; 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); ARTICLE; hcai@pku.edu.cn; 10; 909-922; 48 |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://ir.pku.edu.cn/handle/20.500.11897/493113] |
专题 | 生命科学学院 |
推荐引用方式 GB/T 7714 | Liu, Yuan,Chen, Suting,Pan, Bowen,et al. A subunit vaccine based on rH-NS induces protection against Mycobacterium tuberculosis infection by inducing the Th1 immune response and activating macrophages[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2016. |
APA | Liu, Yuan.,Chen, Suting.,Pan, Bowen.,Guan, Zhu.,Yang, Zhenjun.,...&Cai, Hong.(2016).A subunit vaccine based on rH-NS induces protection against Mycobacterium tuberculosis infection by inducing the Th1 immune response and activating macrophages.ACTA BIOCHIMICA ET BIOPHYSICA SINICA. |
MLA | Liu, Yuan,et al."A subunit vaccine based on rH-NS induces protection against Mycobacterium tuberculosis infection by inducing the Th1 immune response and activating macrophages".ACTA BIOCHIMICA ET BIOPHYSICA SINICA (2016). |
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