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Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Development of tissue inflammation accompanied by NLRP3 inflammasome activation in rabbits infected with Treponema pallidum strain Nichols

Authors: Li-Rong Lin, Yao Xiao, Wei Liu, Yu-Yan Chen, Xiao-Zhen Zhu, Zheng-Xiang Gao, Kun Gao, Man-Li Tong, Hui-Lin Zhang, Shu-Lian Li, Hui-Ling Lin, Wen-Dong Li, Xian-Ming Liang, Yong Lin, Li-Li Liu, Tian-Ci Yang

Published in: BMC Infectious Diseases | Issue 1/2018

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Abstract

Background

The inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum.

Methods

Forty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1β (IL-1β) mRNA analysis during infection. Blood was also collected for the determination of IL-1β concentration.

Results

Rabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1β secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to “normal” levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1β mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1β expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1β in the testes of the infected rabbits.

Conclusions

This study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.
Literature
1.
go back to reference Tong ML, Zhao Q, Liu LL, Zhu XZ, Gao K, Zhang HL, Lin LR, Niu JJ, Ji ZL, Yang TC. Whole genome sequence of the Treponema pallidum subsp. pallidum strain Amoy: An Asian isolate highly similar to SS14. Plos One. 2017;12(8):e0182768.CrossRefPubMedPubMedCentral Tong ML, Zhao Q, Liu LL, Zhu XZ, Gao K, Zhang HL, Lin LR, Niu JJ, Ji ZL, Yang TC. Whole genome sequence of the Treponema pallidum subsp. pallidum strain Amoy: An Asian isolate highly similar to SS14. Plos One. 2017;12(8):e0182768.CrossRefPubMedPubMedCentral
2.
go back to reference Salazar JC, Hazlett KR, Radolf JD. The immune response to infection with Treponema pallidum, the stealth pathogen. Microbes & Infection. 2002;4(11):1133–40.CrossRef Salazar JC, Hazlett KR, Radolf JD. The immune response to infection with Treponema pallidum, the stealth pathogen. Microbes & Infection. 2002;4(11):1133–40.CrossRef
3.
go back to reference Weissleder R, Nahrendorf M, Pittet MJ. Imaging macrophages with nanoparticles. Nat Mater. 2014;13(2):125–38.CrossRefPubMed Weissleder R, Nahrendorf M, Pittet MJ. Imaging macrophages with nanoparticles. Nat Mater. 2014;13(2):125–38.CrossRefPubMed
5.
go back to reference Gross O, Thomas CJ, Guarda G, Tschopp J. The inflammasome: an integrated view. Immunol Rev. 2011;243(1):136–51.CrossRefPubMed Gross O, Thomas CJ, Guarda G, Tschopp J. The inflammasome: an integrated view. Immunol Rev. 2011;243(1):136–51.CrossRefPubMed
6.
go back to reference Wang Y, Wang GZ, Rabinovitch PS, Tabas I. Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-kappaB-mediated inflammation in macrophages. Circ Res. 2014;114(3):421–33.CrossRefPubMed Wang Y, Wang GZ, Rabinovitch PS, Tabas I. Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-kappaB-mediated inflammation in macrophages. Circ Res. 2014;114(3):421–33.CrossRefPubMed
7.
go back to reference Zhang F, Wang L, Wang JJ, Luo PF, Wang XT, Xia ZF. The caspase-1 inhibitor AC-YVAD-CMK attenuates acute gastric injury in mice: involvement of silencing NLRP3 inflammasome activities. Sci Rep. 2016;6:24166.CrossRefPubMedPubMedCentral Zhang F, Wang L, Wang JJ, Luo PF, Wang XT, Xia ZF. The caspase-1 inhibitor AC-YVAD-CMK attenuates acute gastric injury in mice: involvement of silencing NLRP3 inflammasome activities. Sci Rep. 2016;6:24166.CrossRefPubMedPubMedCentral
8.
go back to reference Geldhoff M, Mook-Kanamori BB, Brouwer MC, Troost D, Leemans JC, Flavell RA, Van der Ende A, Van der Poll T, Van de Beek D. Inflammasome activation mediates inflammation and outcome in humans and mice with pneumococcal meningitis. BMC Infect Dis. 2013;13:358.CrossRefPubMedPubMedCentral Geldhoff M, Mook-Kanamori BB, Brouwer MC, Troost D, Leemans JC, Flavell RA, Van der Ende A, Van der Poll T, Van de Beek D. Inflammasome activation mediates inflammation and outcome in humans and mice with pneumococcal meningitis. BMC Infect Dis. 2013;13:358.CrossRefPubMedPubMedCentral
9.
go back to reference Perez-Figueroa E, Torres J, Sanchez-Zauco N, Contreras-Ramos A, Alvarez-Arellano L, Maldonado-Bernal C. Activation of NLRP3 inflammasome in human neutrophils by helicobacter pylori infection. Innate Immun. 2016;22(2):103–12.CrossRefPubMed Perez-Figueroa E, Torres J, Sanchez-Zauco N, Contreras-Ramos A, Alvarez-Arellano L, Maldonado-Bernal C. Activation of NLRP3 inflammasome in human neutrophils by helicobacter pylori infection. Innate Immun. 2016;22(2):103–12.CrossRefPubMed
11.
go back to reference Wei M, Wang L, Wu T, Xi J, Han Y, Yang X, Zhang D, Fang Q, Tang B. NLRP3 activation was regulated by DNA methylation modification during mycobacterium tuberculosis infection. Biomed Res Int. 2016;2016:4323281.PubMedPubMedCentral Wei M, Wang L, Wu T, Xi J, Han Y, Yang X, Zhang D, Fang Q, Tang B. NLRP3 activation was regulated by DNA methylation modification during mycobacterium tuberculosis infection. Biomed Res Int. 2016;2016:4323281.PubMedPubMedCentral
12.
go back to reference Tong ML, Zhang HL, Zhu XZ, Fan JY, Gao K, Lin LR, Liu LL, Li SL, Lin HL, Lin ZF. Re-evaluating the sensitivity of the rabbit infectivity test for Treponema pallidum in modern era. Clin Chim Acta. 2017;464:136–41.CrossRefPubMed Tong ML, Zhang HL, Zhu XZ, Fan JY, Gao K, Lin LR, Liu LL, Li SL, Lin HL, Lin ZF. Re-evaluating the sensitivity of the rabbit infectivity test for Treponema pallidum in modern era. Clin Chim Acta. 2017;464:136–41.CrossRefPubMed
13.
go back to reference Zhang S, Liang X, Zheng X, Huang H, Chen X, Wu K, Wang B, Ma S. Glo1 genetic amplification as a potential therapeutic target in hepatocellular carcinoma. International Journal of Clinical & Experimental Pathology. 2014;7(5):2079–90. Zhang S, Liang X, Zheng X, Huang H, Chen X, Wu K, Wang B, Ma S. Glo1 genetic amplification as a potential therapeutic target in hepatocellular carcinoma. International Journal of Clinical & Experimental Pathology. 2014;7(5):2079–90.
15.
go back to reference Sell S, Gamboa D, Bakerzander SA, Lukehart SA, Miller JN. Host response to Treponema pallidum in intradermally-infected rabbits: evidence for persistence of infection at local and distant sites. J Invest Dermatol. 1980;75(6):470–5.CrossRefPubMed Sell S, Gamboa D, Bakerzander SA, Lukehart SA, Miller JN. Host response to Treponema pallidum in intradermally-infected rabbits: evidence for persistence of infection at local and distant sites. J Invest Dermatol. 1980;75(6):470–5.CrossRefPubMed
16.
17.
go back to reference Seider K, Gerwien F, Kasper L, Allert S, Brunke S, Jablonowski N, Schwarzmuller T, Barz D, Rupp S, Kuchler K, et al. Immune evasion, stress resistance, and efficient nutrient acquisition are crucial for intracellular survival of Candida Glabrata within macrophages. Eukaryot Cell. 2014;13(1):170–83.CrossRefPubMedPubMedCentral Seider K, Gerwien F, Kasper L, Allert S, Brunke S, Jablonowski N, Schwarzmuller T, Barz D, Rupp S, Kuchler K, et al. Immune evasion, stress resistance, and efficient nutrient acquisition are crucial for intracellular survival of Candida Glabrata within macrophages. Eukaryot Cell. 2014;13(1):170–83.CrossRefPubMedPubMedCentral
18.
go back to reference Kaku Y, Imaoka H, Morimatsu Y, Komohara Y, Ohnishi K, Oda H, Takenaka S, Matsuoka M, Kawayama T, Takeya M, et al. Overexpression of CD163, CD204 and CD206 on alveolar macrophages in the lungs of patients with severe chronic obstructive pulmonary disease. PLoS One. 2014;9(1):e87400.CrossRefPubMedPubMedCentral Kaku Y, Imaoka H, Morimatsu Y, Komohara Y, Ohnishi K, Oda H, Takenaka S, Matsuoka M, Kawayama T, Takeya M, et al. Overexpression of CD163, CD204 and CD206 on alveolar macrophages in the lungs of patients with severe chronic obstructive pulmonary disease. PLoS One. 2014;9(1):e87400.CrossRefPubMedPubMedCentral
19.
go back to reference Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, Hoffman HM, Feldstein AE. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology. 2014;59(3):898–910.CrossRefPubMedPubMedCentral Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, Hoffman HM, Feldstein AE. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology. 2014;59(3):898–910.CrossRefPubMedPubMedCentral
20.
go back to reference Mantovani A. The faces of macrophage activation. Eur J Clin Investig. 2013;43:10. Mantovani A. The faces of macrophage activation. Eur J Clin Investig. 2013;43:10.
21.
go back to reference Peeling RW, Hook EW 3rd. The pathogenesis of syphilis: the great mimicker, revisited. J Pathol. 2006;208(2):224–32.CrossRefPubMed Peeling RW, Hook EW 3rd. The pathogenesis of syphilis: the great mimicker, revisited. J Pathol. 2006;208(2):224–32.CrossRefPubMed
22.
go back to reference Schroder K, Zhou RB, Tschopp J. The NLRP3 Inflammasome: a sensor for metabolic danger? Science. 2010;327(5963):296–300.CrossRefPubMed Schroder K, Zhou RB, Tschopp J. The NLRP3 Inflammasome: a sensor for metabolic danger? Science. 2010;327(5963):296–300.CrossRefPubMed
24.
go back to reference Marra C, Sahi S, Tantalo L, Godornes C, Reid T, Behets F, Rompalo A, Klausner JD, Yin Y, Mulcahy F, et al. Enhanced molecular typing of treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis. 2010;202(9):1380–8.CrossRefPubMedPubMedCentral Marra C, Sahi S, Tantalo L, Godornes C, Reid T, Behets F, Rompalo A, Klausner JD, Yin Y, Mulcahy F, et al. Enhanced molecular typing of treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis. 2010;202(9):1380–8.CrossRefPubMedPubMedCentral
Metadata
Title
Development of tissue inflammation accompanied by NLRP3 inflammasome activation in rabbits infected with Treponema pallidum strain Nichols
Authors
Li-Rong Lin
Yao Xiao
Wei Liu
Yu-Yan Chen
Xiao-Zhen Zhu
Zheng-Xiang Gao
Kun Gao
Man-Li Tong
Hui-Lin Zhang
Shu-Lian Li
Hui-Ling Lin
Wen-Dong Li
Xian-Ming Liang
Yong Lin
Li-Li Liu
Tian-Ci Yang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-2993-0

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