Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1β production
| Autor: | Yu-Yan Chen, Zheng-Xiang Gao, Jian-Jun Niu, Li-Li Liu, Zan-Xi Fang, Hui-Lin Zhang, Yong Lin, Yao Xiao, Kun Gao, Li-Rong Lin, Tian-Ci Yang, Man-Li Tong, Wen-Dong Li, Wei Liu, Hui-Ling Lin, Shu-Lian Li, Xiao-Zhen Zhu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS lcsh:Immunologic diseases. Allergy Inflammasomes THP-1 Cells Macrophage Immunology Interleukin-1beta Macrophage polarization 03 medical and health sciences NLRP3 Cell Line Tumor Polarization NLR Family Pyrin Domain-Containing 3 Protein medicine Humans Secretion Syphilis Treponema pallidum Innate immune system integumentary system biology Chemistry Macrophages Interleukin Cell Polarity Inflammasome Macrophage Activation Cathepsins Immunity Innate Cell biology Nitric oxide synthase 030104 developmental biology IL-1β biology.protein lcsh:RC581-607 Reactive Oxygen Species medicine.drug Research Article |
| Zdroj: | BMC Immunology BMC Immunology, Vol 19, Iss 1, Pp 1-9 (2018) |
| ISSN: | 1471-2172 |
| Popis: | Background The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1β production and its influence on macrophage polarization triggered by T. pallidum. Results The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1β and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1β secretion in T. pallidum-treated macrophages, and the observed production of IL-1β occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1β by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1β release from T. pallidum-treated macrophages. Conclusions These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1β secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1β production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection. |
| Databáze: | OpenAIRE |
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