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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

Treponema pallidum (Syphilis) Antigen TpF1 Induces Activation of Macrophages and Accelerates P2X7R-Induced NLRP3-Dependent Release of IL-1β

Author(s): Dong-Ping Lu*, Jie Jia, Shao-Feng Wei, Wei-Lian Zhang, Rui Liang, Ting Liu, Wen-Zhi Yang, Bing-Yan Li, Rong Zhang* and Fen Wang*

Volume 22, Issue 4, 2022

Published on: 11 January, 2022

Page: [425 - 432] Pages: 8

DOI: 10.2174/1871530321666211015091109

Price: $65

Abstract

Background: Syphilis is a chronic infectious disease caused by Treponema pallidum (Tp) infection, which causes local inflammation in the host. TpF1 is an oligomeric protein expressed by the Tp-infected host that can induce the host immune response. There are few studies regarding the role of TpF1 in macrophage activation and the subsequent release of cytokines.

Objective: The objective of this study is to elucidate the effects of TpF1 on the pathological process of Syphilis. In addition, we explored how purinergic 2X7 (P2X7R) induced NOD-like receptor family protein 3 (NLRP3) -dependent release of interleukin-1β (IL-1β) and the underlying mechanisms.

Methods: We explored the influence of TpF1 on cytokine release by macrophages using qRT-PCR and ELISA. The specific phenotype of activated macrophages was determined by flow cytometry.

Results: TpF1 was able to activate macrophages and induce the M1 macrophage phenotype. Moreover, TpF1 activated the NLRP3 inflammasome in macrophages, which was mediated by P2X7R.

Conclusion: The Tp-induced protein TpF1 is able to induce macrophage activation and P2X7R-induced NLRP3-dependent release of IL-1β. Our findings provide a theoretical basis for clarifying the clinical symptoms and pathogenesis of syphilis.

Keywords: Treponema pallidum, TpF1, macrophage, NLRP3, P2X7R, IL-1β.

« Previous Next »
[1]
Ghanem, K.G.; Ram, S.; Rice, P.A. The Modern Epidemic of Syphilis. N. Engl. J. Med., 2020, 382(9), 845-854.
[http://dx.doi.org/10.1056/NEJMra1901593] [PMID: 32101666]
[2]
Radolf, J.D.; Deka, R.K.; Anand, A.; Šmajs, D.; Norgard, M.V.; Yang, X.F. Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen. Nat. Rev. Microbiol., 2016, 14(12), 744-759.
[http://dx.doi.org/10.1038/nrmicro.2016.141] [PMID: 27721440]
[3]
Peeling, R.W.; Mabey, D.; Kamb, M.L.; Chen, X.S.; Radolf, J.D.; Benzaken, A.S. Syphilis. Nat. Rev. Dis. Primers, 2017, 3, 17073.
[http://dx.doi.org/10.1038/nrdp.2017.73] [PMID: 29022569]
[4]
Jiang, H.; Gong, T.; Zhou, R. The strategies of targeting the NLRP3 inflammasome to treat inflammatory diseases. Adv. Immunol., 2020, 145, 55-93.
[http://dx.doi.org/10.1016/bs.ai.2019.11.003] [PMID: 32081200]
[5]
Xu, S.L.; Lin, Y.; Zhu, X.Z.; Liu, D.; Tong, M.L.; Liu, L.L.; Yang, T.C.; Lin, L.R. Autophagy promotes phagocytosis and clearance of Treponema pallidum via the NLRP3 inflammasome in macrophages. J. Eur. Acad. Dermatol. Venereol., 2020, 34(9), 2111-2119.
[http://dx.doi.org/10.1111/jdv.16463] [PMID: 32294266]
[6]
Babolin, C.; Amedei, A.; Ozolins, D.; Zilevica, A.; D’Elios, M.M.; de Bernard, M. TpF1 from Treponema pallidum activates inflammasome and promotes the development of regulatory T cells. J. Immunol., 2011, 187(3), 1377-1384.
[http://dx.doi.org/10.4049/jimmunol.1100615] [PMID: 21709157]
[7]
Pozzobon, T.; Facchinello, N.; Bossi, F.; Capitani, N.; Benagiano, M.; Di Benedetto, G.; Zennaro, C.; West, N.; Codolo, G.; Bernardini, M.; Baldari, C.T.; D’Elios, M.M.; Pellegrini, L.; Argenton, F.; de Bernard, M. Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis through the activation of the IL-8 pathway. Sci. Rep., 2016, 6, 18785.
[http://dx.doi.org/10.1038/srep18785] [PMID: 26728351]
[8]
Lin, L.R.; Liu, W.; Zhu, X.Z.; Chen, Y.Y.; Gao, Z.X.; Gao, K.; Tong, M.L.; Zhang, H.L.; Xiao, Y.; Li, W.D.; Li, S.L.; Lin, H.L.; Liu, L.L.; Fang, Z.X.; Niu, J.J.; Lin, Y.; Yang, T.C. Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1β production. BMC Immunol., 2018, 19(1), 28.
[http://dx.doi.org/10.1186/s12865-018-0265-9] [PMID: 30217146]
[9]
Thumiger, A.; Polenghi, A.; Papinutto, E.; Battistutta, R.; Montecucco, C.; Zanotti, G. Crystal structure of antigen TpF1 from Treponema pallidum. Proteins, 2006, 62(3), 827-830.
[http://dx.doi.org/10.1002/prot.20828] [PMID: 16345079]
[10]
Ho, E.L.; Lukehart, S.A. Syphilis: using modern approaches to understand an old disease. J. Clin. Invest., 2011, 121(12), 4584-4592.
[http://dx.doi.org/10.1172/JCI57173] [PMID: 22133883]
[11]
Arora, N.; Schuenemann, V.J.; Jäger, G.; Peltzer, A.; Seitz, A.; Herbig, A.; Strouhal, M.; Grillová, L.; Sánchez-Busó, L.; Kühnert, D.; Bos, K.I.; Davis, L.R.; Mikalová, L.; Bruisten, S.; Komericki, P.; French, P.; Grant, P.R.; Pando, M.A.; Vaulet, L.G.; Fermepin, M.R.; Martinez, A.; Centurion Lara, A.; Giacani, L.; Norris, S.J.; Šmajs, D.; Bosshard, P.P.; González-Candelas, F.; Nieselt, K.; Krause, J.; Bagheri, H.C. Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster. Nat. Microbiol., 2016, 2, 16245.
[http://dx.doi.org/10.1038/nmicrobiol.2016.245] [PMID: 27918528]
[12]
Lin, L.R.; Gao, Z.X.; Lin, Y.; Zhu, X.Z.; Liu, W.; Liu, D.; Gao, K.; Tong, M.L.; Zhang, H.L.; Liu, L.L.; Xiao, Y.; Niu, J.J.; Liu, F.; Yang, T.C. Akt, mTOR and NF-κB pathway activation in Treponema pallidum stimulates M1 macrophages. Int. Immunopharmacol., 2018, 59, 181-186.
[http://dx.doi.org/10.1016/j.intimp.2018.03.040] [PMID: 29656208]
[13]
Lin, L.R.; Xiao, Y.; Liu, W.; Chen, Y.Y.; Zhu, X.Z.; Gao, Z.X.; Gao, K.; Tong, M.L.; Zhang, H.L.; Li, S.L.; Lin, H.L.; Li, W.D.; Liang, X.M.; Lin, Y.; Liu, L.L.; Yang, T.C. Development of tissue inflammation accompanied by NLRP3 inflammasome activation in rabbits infected with Treponema pallidum strain Nichols. BMC Infect. Dis., 2018, 18(1), 101.
[http://dx.doi.org/10.1186/s12879-018-2993-0] [PMID: 29490620]
[14]
Baker-Zander, S.A.; Lukehart, S.A. Macrophage-mediated killing of opsonized Treponema pallidum. J. Infect. Dis., 1992, 165(1), 69-74.
[http://dx.doi.org/10.1093/infdis/165.1.69] [PMID: 1727898]
[15]
Kubanov, A.; Runina, A.; Deryabin, D. Novel Treponema pallidum Recombinant Antigens for Syphilis Diagnostics: Current Status and Future Prospects. BioMed Res. Int., 2017, 2017, 1436080.
[http://dx.doi.org/10.1155/2017/1436080] [PMID: 28523273]
[16]
Jiang, C.; Zhao, F.; Xiao, J.; Zeng, T.; Yu, J.; Ma, X.; Wu, H.; Wu, Y. Evaluation of the recombinant protein TpF1 of Treponema pallidum for serodiagnosis of syphilis. Clin. Vaccine Immunol., 2013, 20(10), 1563-1568.
[http://dx.doi.org/10.1128/CVI.00122-13] [PMID: 23945159]
[17]
Latz, E.; Duewell, P. NLRP3 inflammasome activation in inflammaging. Semin. Immunol., 2018, 40, 61-73.
[http://dx.doi.org/10.1016/j.smim.2018.09.001] [PMID: 30268598]
[18]
Gross, O.; Thomas, C.J.; Guarda, G.; Tschopp, J. The inflammasome: an integrated view. Immunol. Rev., 2011, 243(1), 136-151.
[http://dx.doi.org/10.1111/j.1600-065X.2011.01046.x] [PMID: 21884173]
[19]
Franceschini, A.; Capece, M.; Chiozzi, P.; Falzoni, S.; Sanz, J.M.; Sarti, A.C.; Bonora, M.; Pinton, P.; Di Virgilio, F. The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB J., 2015, 29(6), 2450-2461.
[http://dx.doi.org/10.1096/fj.14-268714] [PMID: 25690658]
[20]
Gicquel, T.; Robert, S.; Loyer, P.; Victoni, T.; Bodin, A.; Ribault, C.; Gleonnec, F.; Couillin, I.; Boichot, E.; Lagente, V. IL-1β production is dependent on the activation of purinergic receptors and NLRP3 pathway in human macrophages. FASEB J., 2015, 29(10), 4162-4173.
[http://dx.doi.org/10.1096/fj.14-267393] [PMID: 26116704]
[21]
Xu, S.L.; Lin, Y.; Liu, W.; Zhu, X.Z.; Liu, D.; Tong, M.L.; Liu, L.L.; Lin, L.R. The P2X7 receptor mediates NLRP3-dependent IL-1β secretion and promotes phagocytosis in the macrophage response to Treponema pallidum. Int. Immunopharmacol., 2020, 82, 106344.
[http://dx.doi.org/10.1016/j.intimp.2020.106344] [PMID: 32151957]
[22]
Di, A.; Xiong, S.; Ye, Z.; Malireddi, R.K.S.; Kometani, S.; Zhong, M.; Mittal, M.; Hong, Z.; Kanneganti, T.D.; Rehman, J.; Malik, A.B. The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation. Immunity, 2018, 49(1), 56-65.e4.
[http://dx.doi.org/10.1016/j.immuni.2018.04.032] [PMID: 29958799]

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