Skip to main content
Top
Published in: BMC Infectious Diseases 1/2020

01-12-2020 | Sexually Transmitted Infection | Research article

MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis

Authors: Tao Huang, Jun Zhang, Wujian Ke, Xiaohui Zhang, Wentao Chen, Jieyi Yang, Yiwen Liao, Fangwen Liang, Shuqing Mei, Mingjiu Li, Zhenzhou Luo, Qiwei Zhang, Bin Yang, Heping Zheng

Published in: BMC Infectious Diseases | Issue 1/2020

Login to get access

Abstract

Background

Treponema pallidum (T. pallidum) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum.

Methods

In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis.

Results

A total of 74 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states (P < 0.05). One miRNA (hsa-miR-195-5p) showed significant differences between untreated patients and healthy individuals.

Conclusions

This is the first study of miRNA expression differences in peripheral blood mononuclear cells (PBMCs) in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as a non-invasive biomarker of T. pallium infections, which will facilitate better diagnosis and treatment of T. pallium infections.
Appendix
Available only for authorised users
Literature
1.
go back to reference Weinstock GM, Hardham JM, Mcleod MP, Sodergren EJ, Norris SJ. The genome of Treponema pallidum: new light on the agent of syphilis. FEMS Microbiol Rev. 1998;22(4):323–32.CrossRef Weinstock GM, Hardham JM, Mcleod MP, Sodergren EJ, Norris SJ. The genome of Treponema pallidum: new light on the agent of syphilis. FEMS Microbiol Rev. 1998;22(4):323–32.CrossRef
2.
go back to reference Lafond RE, Lukehart SA. Biological basis for syphilis. Clin Microbiol Rev. 2006;19(1):29.CrossRef Lafond RE, Lukehart SA. Biological basis for syphilis. Clin Microbiol Rev. 2006;19(1):29.CrossRef
3.
go back to reference Seña AC, Wolff M, Martin DH, Behets F, Van Damme K, Leone P, et al. Predictors of serological cure and Serofast state after treatment in HIV-negative persons with early syphilis. Clin Infect Dis. 2011;53(11):1092.CrossRef Seña AC, Wolff M, Martin DH, Behets F, Van Damme K, Leone P, et al. Predictors of serological cure and Serofast state after treatment in HIV-negative persons with early syphilis. Clin Infect Dis. 2011;53(11):1092.CrossRef
4.
go back to reference Clement ME, Okeke NL, Hicks CB. Treatment of syphilis: a systematic review. Jama. 2014;312(18):1905–17.CrossRef Clement ME, Okeke NL, Hicks CB. Treatment of syphilis: a systematic review. Jama. 2014;312(18):1905–17.CrossRef
5.
go back to reference Edmondson DG, Hu B, Norris SJ. Long-term in vitro culture of the syphilis spirochete treponema pallidum subsp. pallidum. mBio. 2018;9(3):e01153-18. Edmondson DG, Hu B, Norris SJ. Long-term in vitro culture of the syphilis spirochete treponema pallidum subsp. pallidum. mBio. 2018;9(3):e01153-18.
6.
go back to reference Lukehart SA. Activation of macrophages by products of lymphocytes from normal and syphilitic rabbits. Infect Immun. 1982;37(1):64–9.CrossRef Lukehart SA. Activation of macrophages by products of lymphocytes from normal and syphilitic rabbits. Infect Immun. 1982;37(1):64–9.CrossRef
7.
go back to reference Bouis DA, Popova TG, Takashima A, Norgard MV. Dendritic cells phagocytose and are activated by Treponema pallidum. Infect Immun. 2001;69(1):518–28.CrossRef Bouis DA, Popova TG, Takashima A, Norgard MV. Dendritic cells phagocytose and are activated by Treponema pallidum. Infect Immun. 2001;69(1):518–28.CrossRef
8.
go back to reference Engelkens HJ, ten Kate FJ, Judanarso J, Vuzevski VD, van Lier JB, Godschalk JC, et al. The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws. Genitourin Med. 1993;69(2):102–7.PubMedPubMedCentral Engelkens HJ, ten Kate FJ, Judanarso J, Vuzevski VD, van Lier JB, Godschalk JC, et al. The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws. Genitourin Med. 1993;69(2):102–7.PubMedPubMedCentral
9.
go back to reference Van Voorhis WC, Barrett LK, Koelle DM, Nasio JM, Plummer FA, Lukehart SA. Primary and secondary syphilis lesions contain mRNA for Th1 cytokines. J Infect Dis. 1996;173(2):491–5.CrossRef Van Voorhis WC, Barrett LK, Koelle DM, Nasio JM, Plummer FA, Lukehart SA. Primary and secondary syphilis lesions contain mRNA for Th1 cytokines. J Infect Dis. 1996;173(2):491–5.CrossRef
10.
go back to reference Arroll TW, Centurionlara A, Lukehart SA, Voorhis WCV. T-cell responses to Treponema pallidumsubsp. Pallidum antigens during the course of experimental syphilis infection. Infect Immun. 1999;67(9):4757–63.CrossRef Arroll TW, Centurionlara A, Lukehart SA, Voorhis WCV. T-cell responses to Treponema pallidumsubsp. Pallidum antigens during the course of experimental syphilis infection. Infect Immun. 1999;67(9):4757–63.CrossRef
11.
go back to reference Podwinska J, Lusiak M, Zaba R, Bowszyc J. The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease. Fems Immunol Med Microbiol. 2000;28(1):1–14.CrossRef Podwinska J, Lusiak M, Zaba R, Bowszyc J. The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease. Fems Immunol Med Microbiol. 2000;28(1):1–14.CrossRef
12.
go back to reference Zhao J, Jie MA, Zhang X, Qing LI, Yang X. Equilibrium of Treg/Th17 cells of peripheral blood in syphilitic patients with sero-resistance. Exp Ther Med. 2016;11(6):2300–4.CrossRef Zhao J, Jie MA, Zhang X, Qing LI, Yang X. Equilibrium of Treg/Th17 cells of peripheral blood in syphilitic patients with sero-resistance. Exp Ther Med. 2016;11(6):2300–4.CrossRef
13.
go back to reference Parmila V, Pandey RK, Priyanka P, Prajapati VK. Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Human Infectious Diseases. Front Microbiol. 2016;7(117):1274. Parmila V, Pandey RK, Priyanka P, Prajapati VK. Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Human Infectious Diseases. Front Microbiol. 2016;7(117):1274.
14.
go back to reference Keck J, Gupta R, Christenson LK, Arulanandam BP. MicroRNA mediated regulation of immunity against gram-negative bacteria. Int Rev Immunol. 2017;7014:1. Keck J, Gupta R, Christenson LK, Arulanandam BP. MicroRNA mediated regulation of immunity against gram-negative bacteria. Int Rev Immunol. 2017;7014:1.
15.
go back to reference Houzet L, Man LY, Lame VD, Desai D, Smith SM, Jeang KT. MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1) seropositive individuals. Retrovirology. 2008;5(1):118.CrossRef Houzet L, Man LY, Lame VD, Desai D, Smith SM, Jeang KT. MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1) seropositive individuals. Retrovirology. 2008;5(1):118.CrossRef
16.
go back to reference Masotti A, Donninelli G, Sacco LD, Varano B, Cornò MD, Gessani S. HIV-1 gp120 influences the expression of microRNAs in human monocyte-derived dendritic cells via STAT3 activation. BMC Genomics. 2015;16(1):480.CrossRef Masotti A, Donninelli G, Sacco LD, Varano B, Cornò MD, Gessani S. HIV-1 gp120 influences the expression of microRNAs in human monocyte-derived dendritic cells via STAT3 activation. BMC Genomics. 2015;16(1):480.CrossRef
17.
go back to reference Zhang X, Guo J, Fan S, Li Y, Wei L, Yang X, Jiang T, Chen Z, Wang C, Liu J. Screening and identification of six serum microRNAs as novel potential combination biomarkers for pulmonary tuberculosis diagnosis. Plos One. 2013;8(12):e81076.CrossRef Zhang X, Guo J, Fan S, Li Y, Wei L, Yang X, Jiang T, Chen Z, Wang C, Liu J. Screening and identification of six serum microRNAs as novel potential combination biomarkers for pulmonary tuberculosis diagnosis. Plos One. 2013;8(12):e81076.CrossRef
18.
go back to reference Lochhead RB, Zachary JF, Dalla RL, Ma Y, Weis JH, O'Connell RM, Weis JJ. Antagonistic interplay between MicroRNA-155 and IL-10 during Lyme Carditis and arthritis. PLoS One. 2015;10(8):e0135142.CrossRef Lochhead RB, Zachary JF, Dalla RL, Ma Y, Weis JH, O'Connell RM, Weis JJ. Antagonistic interplay between MicroRNA-155 and IL-10 during Lyme Carditis and arthritis. PLoS One. 2015;10(8):e0135142.CrossRef
19.
go back to reference Lu P, Fang C, Cheng Q, Ke WJ, Huang T, Zhang J, et al. Serum microRNA profiles in patients with syphilis. J Eur Acad Dermatol Venereol. 2017;31(7):e326–e328.CrossRef Lu P, Fang C, Cheng Q, Ke WJ, Huang T, Zhang J, et al. Serum microRNA profiles in patients with syphilis. J Eur Acad Dermatol Venereol. 2017;31(7):e326–e328.CrossRef
20.
go back to reference Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. 2012;14(2):147.CrossRef Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. 2012;14(2):147.CrossRef
21.
go back to reference Jay C, Nemunaitis J, Chen P, Fulgham P, Tong AW. miRNA profiling for diagnosis and prognosis of human cancer. Dna Cell Biol. 2007;26(5):293.CrossRef Jay C, Nemunaitis J, Chen P, Fulgham P, Tong AW. miRNA profiling for diagnosis and prognosis of human cancer. Dna Cell Biol. 2007;26(5):293.CrossRef
22.
go back to reference Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, et al. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol. 2011;48(1):61.CrossRef Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, et al. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol. 2011;48(1):61.CrossRef
23.
go back to reference Shi W, Du J, Qi Y, Liang G, Wang T, Li S, et al. Aberrant expression of serum miRNA in schizophrenia. J Psychiatr Res. 2012;46(2):198–204.CrossRef Shi W, Du J, Qi Y, Liang G, Wang T, Li S, et al. Aberrant expression of serum miRNA in schizophrenia. J Psychiatr Res. 2012;46(2):198–204.CrossRef
24.
go back to reference Ji F, Yang B, Peng X, Ding H, You H, Tien P. Circulating microRNAs in hepatitis B virus-infected patients. J Viral Hepat. 2011;18(7):242–51.CrossRef Ji F, Yang B, Peng X, Ding H, You H, Tien P. Circulating microRNAs in hepatitis B virus-infected patients. J Viral Hepat. 2011;18(7):242–51.CrossRef
25.
go back to reference Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007;120(5):1046.CrossRef Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007;120(5):1046.CrossRef
26.
go back to reference Brinkman MB, Mcgill MA, Pettersson J, Rogers A, Matejkovã P, Smajs D, et al. A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin. Infect Immun. 2008;76(5):1848–57.CrossRef Brinkman MB, Mcgill MA, Pettersson J, Rogers A, Matejkovã P, Smajs D, et al. A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin. Infect Immun. 2008;76(5):1848–57.CrossRef
27.
go back to reference Cameron CE, Brown EL, Kuroiwa JM, Schnapp LM, Brouwer NL. Treponema pallidum fibronectin-binding proteins. J Bacteriol. 2004;186(20):7019–22.CrossRef Cameron CE, Brown EL, Kuroiwa JM, Schnapp LM, Brouwer NL. Treponema pallidum fibronectin-binding proteins. J Bacteriol. 2004;186(20):7019–22.CrossRef
28.
go back to reference Cruz AR, Ramirez LG, Zuluaga AV, Pillay A, Abreu C, Valencia CA, et al. Immune evasion and recognition of the syphilis spirochete in blood and skin of secondary syphilis patients: two immunologically distinct compartments. PLoS Negl Trop Dis. 2012;6(7):e1717.CrossRef Cruz AR, Ramirez LG, Zuluaga AV, Pillay A, Abreu C, Valencia CA, et al. Immune evasion and recognition of the syphilis spirochete in blood and skin of secondary syphilis patients: two immunologically distinct compartments. PLoS Negl Trop Dis. 2012;6(7):e1717.CrossRef
29.
go back to reference He JF, Luo YM, Wan XH, Jiang D. Biogenesis of MiRNA-195 and its role in biogenesis, the cell cycle, and apoptosis. J Biochem Mol Toxicol. 2011;25(6):404.CrossRef He JF, Luo YM, Wan XH, Jiang D. Biogenesis of MiRNA-195 and its role in biogenesis, the cell cycle, and apoptosis. J Biochem Mol Toxicol. 2011;25(6):404.CrossRef
30.
go back to reference Zheng D, Yu Y, Li M, Wang G, Chen R, Fan GC, et al. Inhibition of miR-195 prevents apoptosis and multiple-organ injury in mouse models of sepsis. J Infect Dis. 2016;213(10):1661.CrossRef Zheng D, Yu Y, Li M, Wang G, Chen R, Fan GC, et al. Inhibition of miR-195 prevents apoptosis and multiple-organ injury in mouse models of sepsis. J Infect Dis. 2016;213(10):1661.CrossRef
31.
go back to reference Chen YQ, Wang XX, Yao XM, Zhang DL, Yang XF, Tian SF, et al. MicroRNA-195 promotes apoptosis in mouse Podocytes via enhanced Caspase activity driven by BCL2 insufficiency. Am J Nephrol. 2011;34(6):549.CrossRef Chen YQ, Wang XX, Yao XM, Zhang DL, Yang XF, Tian SF, et al. MicroRNA-195 promotes apoptosis in mouse Podocytes via enhanced Caspase activity driven by BCL2 insufficiency. Am J Nephrol. 2011;34(6):549.CrossRef
32.
go back to reference Zheng D, Ma J, Yu Y, Li M, Ni R, Wang G, et al. Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice. Diabetologia. 2015;58(8):1949.CrossRef Zheng D, Ma J, Yu Y, Li M, Ni R, Wang G, et al. Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice. Diabetologia. 2015;58(8):1949.CrossRef
33.
go back to reference Bras JP, Silva AM, Calin GA, Barbosa MA, Santos SG, Almeida MI. miR-195 inhibits macrophages pro-inflammatory profile and impacts the crosstalk with smooth muscle cells. Plos One. 2017;12(11):e0188530.CrossRef Bras JP, Silva AM, Calin GA, Barbosa MA, Santos SG, Almeida MI. miR-195 inhibits macrophages pro-inflammatory profile and impacts the crosstalk with smooth muscle cells. Plos One. 2017;12(11):e0188530.CrossRef
34.
go back to reference Wang J, Wu J, Cheng Y, Jiang Y, Li G. Over-expression of microRNA-223 inhibited the proinflammatory responses in helicobacter pylori-infection macrophages by down-regulating IRAK-1. Am J Transl Res. 2016;8(2):615.PubMedPubMedCentral Wang J, Wu J, Cheng Y, Jiang Y, Li G. Over-expression of microRNA-223 inhibited the proinflammatory responses in helicobacter pylori-infection macrophages by down-regulating IRAK-1. Am J Transl Res. 2016;8(2):615.PubMedPubMedCentral
Metadata
Title
MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis
Authors
Tao Huang
Jun Zhang
Wujian Ke
Xiaohui Zhang
Wentao Chen
Jieyi Yang
Yiwen Liao
Fangwen Liang
Shuqing Mei
Mingjiu Li
Zhenzhou Luo
Qiwei Zhang
Bin Yang
Heping Zheng
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2020
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-020-4846-x

Other articles of this Issue 1/2020

BMC Infectious Diseases 1/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.