The combination of maltose-binding protein and BCG-induced Th1 activation is involved in TLR2/9-mediated upregulation of MyD88-TRAF6 and TLR4-mediated downregulation of TRIF-TRAF3
| Autor: | Xiaoyu Zhai, Guomu Liu, Nannan Zhang, Xiaoyu Yang, Guixiang Tai, Weihua Ni, Hongyue Zhou |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
CD4-Positive T-Lymphocytes
Transcriptional Activation 0301 basic medicine TRAF3 Immunology Down-Regulation Biology Maltose-Binding Proteins Mice 03 medical and health sciences Maltose-binding protein Downregulation and upregulation Animals TNF Receptor-Associated Factor 6 TNF Receptor-Associated Factor 3 TLR9 Th1 Cells Toll-Like Receptor 2 In vitro Up-Regulation Cell biology Mice Inbred C57BL Toll-Like Receptor 4 Adaptor Proteins Vesicular Transport TLR2 030104 developmental biology TRIF Myeloid Differentiation Factor 88 TLR4 biology.protein Cytokines Signal Transduction |
| Zdroj: | Cellular Immunology. 325:56-63 |
| ISSN: | 0008-8749 |
| DOI: | 10.1016/j.cellimm.2018.02.006 |
| Popis: | Our previous study demonstrated that maltose-binding protein (MBP) activated Th1 through the TLR2-mediated MyD88-dependent pathway and the TLR4-mediated TRIF-dependent pathway. The combination of MBP and BCG synergistically induced Th1 activation, and the TLR2/9-mediated MyD88-dependent pathway is involved in this process. To further explore this mechanism, we stimulated purified mouse CD4+ T cells with MBP and BCG in vitro. The results demonstrated that MBP combined with BCG synergistically increased IFN-γ production and TLR2/4/9 expression, suggesting the involvement of TLR2/4/9 in the combination-induced Th1 activation. Next, TLRs 2/4/9 were blocked to analyze the effects of TLRs on Th1 activation. The results demonstrated that MBP induced a low level of Th1 activation by upregulating TLR2-mediated MyD88-TRAF6 and TLR4-mediated TRIF-TRAF3 expression, whereas MBP combined with BCG induced synergistic Th1 activation, which was not only triggered by strong upregulation of TLR2/9-mediated MyD88-TRAF6 expression but also by shifting TLR4-mediated TRIF-TRAF3 into the TRIF-TRAF6 pathway. Moreover, we observed that a TLR4 antibody upregulated MyD88 expression and a TLR9 inhibitor downregulated TRIF expression, indicating that there was cross-talk between TLRs 2/4/9 in MBP combined with BCG-induced Th1 activation. Our findings may expand the knowledge regarding TLR cross-talk involved in regulating the Th1 response. |
| Databáze: | OpenAIRE |
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