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. 2020 Feb 22;20(1):165.
doi: 10.1186/s12879-020-4846-x.

MicroRNA Expression Profiling of Peripheral Blood Mononuclear Cells Associated With Syphilis

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Free PMC article

MicroRNA Expression Profiling of Peripheral Blood Mononuclear Cells Associated With Syphilis

Tao Huang et al. BMC Infect Dis. .
Free PMC article

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.

Keywords: Peripheral blood mononuclear cells; Sexually transmitted infections; Syphilis; Treponema pallidum; microRNA profiling.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Principal component analysis (PCA) of miRNA expression data from human peripheral blood mononuclear cells (PBMCs). Red, A1-A6, healthy individuals; yellow, B1-B6, serofast state patients; green, C1-C6, syphilis patients before treatment; blue, D1-D6, serologically cured patients
Fig. 2
Fig. 2
miRNA screening in healthy individuals(A1-A6), syphilitic patients (C1-C6), serofast patients (B1-B6), and serologically cured patients (D1-D6). Red boxes indicate up-regulated miRNAs, and purple boxes indicate down-regulated miRNAs. The brightness indicates the magnitude of the difference. Changes in miRNA expression (FC > =1.5, P < 0.05) are illustrated by the heat map. For interpretation of the colors in this figure legend, the reader is referred to the web version of this article. a Comparison of syphilitic patients and healthy individuals, b Comparison of serofast patients and serologically cured patients
Fig. 3
Fig. 3
Pathway analysis. The top 17 most significantly changed pathways associated with target genes. The Y-axis shows the negative logarithm of the P value (−lg p), and the blue bars show the changed pathways
Fig. 4
Fig. 4
MicroRNA-gene network. The microRNA-gene network demonstrated that the predicted target genes were regulated by miRNAs. Square grid nodes represent microRNAs, cycle nodes represent target genes, red indicates upregulated genes, and blue indicates downregulated genes. The size of the circle or square represents the degree value. Larger circles are associated with miRNAs that play more critical roles in regulation. a Red represents syphilitic patients up-regulated relative to healthy individuals, blue opposite. b Red represents serologically cured patients up-regulated relative to serofast state, blue opposite
Fig. 5
Fig. 5
a Detection of PBMCs of different stages miRNAs by the RT-qPCR assay. The expression of eight miRNAs was measured in 106 samples. We analyzed the expression of eight miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p, hsa-miR-342-3p, hsa-miR-6511a-3p, hsa-miR-31-5p, hsa-miR-6855-3p) selected from the microarray data by using RT-PCR. Relative expression was used to normalize the relative gene expression data in the RT-qPCR assay. U6 was set as the reference gene. Statistical analysis was performed using the nonparametric Mann-Whitney test. ***P < 0.001, **P < 0.01, *P < 0.05. b PBMCs from healthy individuals were incubated with T. pallidum, and the expression of eight miRNAs was measured by RT-PCR

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